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Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56 years), serum creatinine 127 (101–153) µmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1–3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15–22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106–159) µmol/L post-COVID-19 infection and 128 (101–161) µmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection. [ABSTRACT FROM AUTHOR]

Introduction: The discovery of new drugs is crucial for pharmaceutical research, development and patient care. One way to achieve this goal is by repurposing existing pharmaceuticals, which can provide valuable insights into their development trends and aid in the systematic creation of new drugs. The FDA's CDER (Center for Drug Evaluation and Research) compiles an annual summary of novel pharmaceuticals, some of which are truly unique and contribute to the advancement of therapeutic therapy. We examined the FDA's trends in medicine approval over the past 50 years. We compiled data on the number of new pharmaceuticals developed between 2019 and 2023, including the number of anti-viral drugs. I presented the graphs and analyzed the reasons for medication rejections before concluding. Aim: This project aims to study and analyze the list of Anti-viral drugs Approved by USFDA From 2019-2023. Background: The United States Food and Drug Administration (USFDA) has developed and approved antiviral medications at a significantly faster pace in recent years in response to the ongoing threat that various viral diseases offer to the world. Effective therapies against both recognized and developing viral infections are desperately needed and the pharmaceutical sector has shown a remarkable commitment to meeting this need between 2019 and 2023. Materials and Methods: The study gathered data from the FDA's online database on innovative medicine approvals between 2019 and 2023. Results: Out of the 216 new pharmaceuticals approved in the last five years, just 24 are biologics. According to these results, fewer Investigational New Drug Applications (INDAs) are being filed under the antiviral and antibiotic categories. Conclusion: Our findings show that upholding safety and efficacy requirements is essential to the development of new pharmaceuticals. Our analysis also clarifies the causes of drug rejections, highlighting the need to follow FDA guidelines to avert regulatory action. [ABSTRACT FROM AUTHOR]

Aim: The proposed study was to establish a Greener method and validation, by green chromatography technique for combined anti-viral drugs, measuring greenness using various tools, which is one of the emerging developments in the analytical field. Materials and Methods: The chromatographic separation is achieved by using C (250x4.6, 5 μm) column by applying isocratic elution using the mobile phase containing Ethanol and Isopropyl acetate in the ratio of (55:45% v/v) with 1 mL/min flow rate. Results: The separation of drugs is achieved by using greener mobile phase.The Retention time of 1.854 min and 9.09 min for Ritonavir and Ombitasvir was found respectively. The regression co-efficient (R2) is 0.987 for the both drugs. Accuracy and precision is evaluated for the method and found be within the limit and the results were reproducible. Assessment of method was carried out using the three different tools. The developed method is anticipated to be eco-friendly, alternative to developed method UPLC method in regard to safe solvent, less toxic and less run time. The Proposed method was found suitable for the simultaneous estimation in their combined dosage form. [ABSTRACT FROM AUTHOR]

Context: Recently, a few antiviral drugs viz Molnupiravir (EIDD-1931), Favipiravir, Ribavirin, Sofosbuvir, Galidesivir, and Remdesivir are shown to be beneficial against COVID-19 disease. These drugs bind to the viral RNA single strand to inhibit the virus genome replication. Similarly, recently, some artificial nucleotides, such as P, J, B, X, Z, V, S, and K were proposed to behave as potent antiviral candidates. However, their activity in the presence of the most reactive hydroxyl (OH) radical is not yet known. Here, the possibility of RNA strand break due to the OH radical-induced C1′-hydrogen (H) abstraction reaction of the above molecules (except Remdesivir) is studied in detail by considering their nucleotide conformation. The results are compared with those of the natural RNA nucleotides (G, C, A, and U). Due to low Gibbs barrier-free energy and high exothermicity, all these nucleotides (except Remdesivir) are prone to OH radical-induced C1′-H abstraction reaction. As Remdesivir contains a C1′-CN bond, the OH radical substitution reactions at the CN and C1′ sites would likely liberate the catalytically important CN group, thereby downgrading its activity. Method: Initially, the B3LYP-D3 dispersion-corrected density functional theory method and 6–31 + G* basis set were used to optimize all reactant, transition state, and product complexes in the implicit aqueous medium. Subsequently, the structures of these complexes were further optimized by using the ωB97X-D dispersion-corrected density functional theory method and cc-PVTZ basis set in the aqueous medium. The IEFPCM method was used to model the aqueous medium. [ABSTRACT FROM AUTHOR]

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The COVID-19 pandemic, instigated by the emergence of the novel coronavirus, SARS-CoV-2, created an incomparable global health crisis. Due to its highly virulent nature, identifying potential therapeutic agents against this lethal virus is crucial. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. To expedite the search for potential therapeutic candidates, this review delved into computational studies. Recent investigations have harnessed computational methods to identify promising inhibitors targeting PLpro, aiming to suppress the viral activity. Molecular docking techniques were employed by researchers to explore the binding sites for antiviral drugs within the catalytic region of PLpro. The review elucidates the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Through comprehensive all-atom molecular dynamics (MD) simulations, the stability of drug–PLpro complexes was assessed, providing dynamic insights into their interactions. By evaluating binding energy estimates from MD simulations, stable drug–PLpro complexes with potential antiviral properties were identified. This review offers a comprehensive overview of the potential drug/lead candidates discovered thus far against PLpro using diverse in silico methodologies, encompassing drug repurposing, structure-based, and ligand-based virtual screenings. Additionally, the identified drugs are listed based on their chemical structures and meticulously examined according to various structural parameters, such as the estimated binding free energy (ΔG), types of intermolecular interactions, and structural stability of PLpro–ligand complexes, as determined from the outcomes of the MD simulations. Underscoring the pivotal role of targeting SARS-CoV-2 PLpro in the battle against COVID-19, this review establishes a robust foundation for identifying promising antiviral drug candidates by integrating molecular dynamics simulations, structural modeling, and computational insights. The continual imperative for the improvement of existing drugs and exploring novel compounds remains paramount in the global efforts to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, underscoring the interdisciplinary synergy crucial to this endeavor. [ABSTRACT FROM AUTHOR]

Human coronaviruses are a continuous threat to the human population and have limited antiviral treatments, and the recent COVID-19 pandemic sparked interest in finding new antiviral strategies, such as natural products, to combat emerging coronaviruses. Rapid efforts in the scientific community to identify effective antiviral agents for coronaviruses remain a focus to minimize mortalities and global setbacks. In this study, an essential oil derived from Myrtus communis L. (MEO) is effective against HCoV-229E and HCoV-OC43 virus infections in comparison to two FDA-approved drugs, Remdesivir and Nirmatrelvir. Gas-chromatography and mass spectrometry were used to identify the chemical composition of MEO. Slight antioxidant activity was observed in MEO, indicating a role in oxidative stress. A dose–response curve measuring the EC50 indicates a high potency against HCoV-229E and HCoV-OC43 virus infections on Huh7.5 cells with low cytotoxicity using a PrestoBlue cell viability assay. Our findings demonstrate that MEO exhibits potent antiviral activity against HCoV-229E and HCoV-OC43 on Huh7.5 cells within a low-cytotoxicity range, but not on SARS-CoV-2. Artificial bacterial chromosome plasmids that expressed SARS-CoV-2 used for replicon—to determine viral replication and viral assembly/egress on HEK293T/17 cells—and virus-like particles on Huh7.5-AT cells—to determine viral entry and assembly/egress—showed no antiviral activity with MEO in comparison to Remdesivir. This study reveals the potential effectiveness of MEO as an alternative natural remedy to treat human coronaviruses and a potential antiviral agent for future coronavirus infections. [ABSTRACT FROM AUTHOR]

The porcine enteric coronaviruses (PECs) currently reported include porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), transmissible gastroenteritis virus (TGEV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). In the absence of effective treatment, they can cause similar clinical characteristics including weight loss, sleepiness, vomiting, anorexia and fatal diarrhea in neonatal piglets, resulting in significant economic losses to the global pig industry. Although many studies on drugs for treating and combating PECs have been issued. There are still no specific drug targeting PECs and used in clinical production. Therefore, it is necessary to sort out and summarize the research on the treatment and anti PECs drugs, and further development of low toxicity and high efficiency drugs is needed. Here, we review the latest progress of anti PECs drugs, focus on the mechanism of anti PECs reaction of drug components, and try to clarify new strategies for effective control and elimination of PECs. These comprehensive and profound insights will help to further investigate, prevent and control the transmission of PECs infection.

Objectives. To describe the pharmaceutical technology of controlled degradation of protein molecules (PROTAC®, Proteolysis Targeting Chimera), approaches to the design of the PROTAC® molecule, methods of ligand and linker selection and synthesis, as well as the application of this technology in dealing with a variety of diseases and the possible limitations of its use.Results. The review covers 77 sources, mostly from 2020–2023. The review outlines the principle of PROTAC® technology: the construction of a chimeric molecule consisting of three fragments. One fragment specifically binds to the biotarget, another recruits the proteolytic system of the host cell, and the third binds them together. The main areas of the current development of the technology are described herein, as well as the opportunities and limitations of chimeric molecules in the fight against different types of infectious diseases.Conclusion. The potential to use PROTAC® technology to combat cancer as well as neurodegenerative, autoimmune, and infectious diseases is shown.

Abstract Coronaviruses employ various strategies for survival, among which the activation of endogenous or exogenous apoptosis stands out, with viral proteins playing a pivotal role. Notably, highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV exhibit a greater array of non-structural proteins compared to low-pathogenic strains, facilitating their ability to induce apoptosis via multiple pathways. Moreover, these viral proteins are adept at dampening host immune responses, thereby bolstering viral replication and persistence. This review delves into the intricate interplay between highly pathogenic coronaviruses and apoptosis, systematically elucidating the molecular mechanisms underpinning apoptosis induction by viral proteins. Furthermore, it explores the potential therapeutic avenues stemming from apoptosis inhibition as antiviral agents and the utilization of apoptosis-inducing viral proteins as therapeutic modalities. These insights not only shed light on viral pathogenesis but also offer novel perspectives for cancer therapy.

Influenza is an acute respiratory viral infection, known for its epidemics and pandemics, claiming millions of lives everywhere. Influenza A virus (Orthomyxoviridae family), whose genome consists of 8 RNA segments of negative polarity, is widespread due to its patterns of variability, which determine the development of resistance, for example, to antiviral drugs. Reassortment mechanisms and point mutations in the influenza A virus genome can lead to a great variety of different variants of this pathogen. The considered life cycle of the influenza A virus with a detailed description of the molecular genetic features of its structures allows us to highlight the advantages and disadvantages of the etiotropic therapy used, affecting different stages of virus replication from the point of view of evidence-based medicine in aspects related to its resistance.

Abstract The ongoing COVID-19 pandemic continues to pose significant challenges worldwide, despite widespread vaccination. Researchers are actively exploring antiviral treatments to assess their efficacy against emerging virus variants. The aim of the study is to employ M-polynomial, neighborhood M-polynomial approach and QSPR/QSAR analysis to evaluate specific antiviral drugs including Lopinavir, Ritonavir, Arbidol, Thalidomide, Chloroquine, Hydroxychloroquine, Theaflavin and Remdesivir. Utilizing degree-based and neighborhood degree sum-based topological indices on molecular multigraphs reveals insights into the physicochemical properties of these drugs, such as polar surface area, polarizability, surface tension, boiling point, enthalpy of vaporization, flash point, molar refraction and molar volume are crucial in predicting their efficacy against viruses. These properties influence the solubility, permeability, and bio availability of the drugs, which in turn affect their ability to interact with viral targets and inhibit viral replication. In QSPR analysis, molecular multigraphs yield notable correlation coefficients exceeding those from simple graphs: molar refraction (MR) (0.9860), polarizability (P) (0.9861), surface tension (ST) (0.6086), molar volume (MV) (0.9353) using degree-based indices, and flash point (FP) (0.9781), surface tension (ST) (0.7841) using neighborhood degree sum-based indices. QSAR models, constructed through multiple linear regressions (MLR) with a backward elimination approach at a significance level of 0.05, exhibit promising predictive capabilities highlighting the significance of the biological activity $$IC_{50}$$ I C 50 (Half maximal inhibitory concentration). Notably, the alignment of predicted and observed values for Remdesivir’s with obs $${pIC_{50} = 6.01}$$ p I C 50 = 6.01 ,pred $${pIC_{50} = 6.01}$$ p I C 50 = 6.01 ( $$pIC_{50}$$ p I C 50 represents the negative logarithm of $$IC_{50}$$ I C 50 ) underscores the accuracy of multigraph-based QSAR analysis. The primary objective is to showcase the valuable contribution of multigraphs to QSPR and QSAR analyses, offering crucial insights into molecular structures and antiviral properties. The integration of physicochemical applications enhances our understanding of factors influencing antiviral drug efficacy, essential for combating emerging viral strains effectively.

Viral infections usually induce the rearrangement of cellular cytoskeletal proteins and organelle membrane structures, thus creating independent compartments [termed replication organelles (ROs)] to facilitate viral genome replication. Within the ROs, viral replicases, including polymerases, helicases, and ligases, play functional roles during viral replication. These viral replicases are pivotal in the virus life cycle, and numerous studies have demonstrated that the viral replicases could be the potential targets for drugs development. Here, we summarize primarily the key replicases within viral ROs and emphasize the advancements of antiviral drugs targeting crucial viral replicases, providing novel insights into the future development of antiviral strategies. [ABSTRACT FROM AUTHOR]

An automated flow analysis-solid phase extraction (FA-SPE) system and methodology of ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) analysis were developed for the determination of selected antiviral drugs (acyclovir, amantadine, rimantadine, and oseltamivir) in water samples. The proposed FA-SPE approach enables the integration of various extraction stages and elimination of the sample evaporation step and offers individual customisation of SPE parameters, inter alia sample, and eluate flow rate and volume. Using the developed FA-SPE procedure, e.g. a 100-fold preconcentration of the target analytes in 1 h was achieved. A method for chromatographic analysis was also developed to determine the selected antiviral drugs in combination with the use of the FA-SPE system. The developed FA-SPE UHPLC-MS/MS method was validated including the determination of linearity of analytical graphs, limits of detection (5.5–99.9 pg mL−1) and quantification (18.3–329.8 pg mL−1), intra-day (1.8–8.3%) and inter-day (3.0–9.2%) precision, recovery (95.6–105.3%), and matrix effects (− 12.9 to 13.2%). The proposed method was successfully applied to analyse tap, drinking, and river water samples, revealing the presence of amantadine at a concentration of 40.1 pg mL−1 in one sample. The environmental impact of the developed FA-SPE sample preparation procedure was also assessed using the AGREEprep metric tool and compared with five other literature methods, achieving the most sustainable outcome. [ABSTRACT FROM AUTHOR]

Carriers of herpes simplex virus type 1 (HSV-1) account for more than 90% of the global population. Infection manifests itself in the formation of blisters and ulcers on the face or genitals and can cause blindness, encephalitis, and generalized infection. All first- and second-line modern antiherpetic drugs selectively inhibit viral DNA polymerase. The purine–benzoxazine conjugate LAS-131 ((S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine), which we have described earlier, uses the large subunit of the HSV-1 terminase complex as a biotarget and selectively inhibits HSV-1 reproduction in vitro. Basically new results were for the first time obtained to characterize the combined effect on human herpesvirus infection for LAS-131 used in combination with practically significant antiviral compounds, including the nucleoside analogs acyclovir (ACV), penciclovir (PCV), ganciclovir (GCV), brivudine (BVdU), iododeoxyuridine (IdU), and adenine arabinoside (Ara-A); the nucleoside phosphonate analog cidofovir (CDV); and the pyrophosphate analog foscarnet (FOS). A cytopathic effect (CPE) inhibition assay showed that the drug concentration that inhibited the virus-induced CPE by 50% decreased by a factor of 2 (an additive effect, FOS) or more (a synergistic effect; ACV, PCV, GCV, IdU, BVdU, Ara-A, and CDV) when the drugs were used in combination with LAS-131. Nonpermissive conditions for HSV-1 reproduction were thus created at lower drug concentrations, opening up new real possibilities to control human herpesvirus infection. [ABSTRACT FROM AUTHOR]

Background: The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations. Aim: To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among mainly vaccinated community-based people at higher risk of severe outcomes from COVID-19 over 6 months. Design and setting: An economic evaluation of the PANORAMIC trial in the UK. Method: A cost-utility analysis that adopted a UK NHS and personal social services perspective and a 6-month time horizon was performed using PANORAMIC trial data. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity and subgroup analyses assessed the impacts of uncertainty and heterogeneity. Threshold analysis explored the price for molnupiravir consistent with likely reimbursement. Results: In the base-case analysis, molnupiravir had higher mean costs of £449 (95% confidence interval [CI] = 445 to 453) and higher mean QALYs of 0.0055 (95% CI = 0.0044 to 0.0067) than usual care (mean incremental cost per QALY of £81 190). Sensitivity and subgroup analyses showed similar results, except for those aged ≥75 years, with a 55% probability of being cost-effective at a £30 000 per QALY threshold. Molnupiravir would have to be priced around £147 per course to be cost-effective at a £15 000 per QALY threshold. Conclusion: At the current cost of £513 per course, molnupiravir is unlikely to be cost-effective relative to usual care over a 6-month time horizon among mainly vaccinated patients with COVID-19 at increased risk of adverse outcomes, except those aged ≥75 years. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause significant economic losses to the global swine industry, yet effective prevention and control measures remain elusive. The development of novel antivirals is thus urgently needed. Rifampicin (RFP), a semisynthetic derivative of rifamycin, has been previously reported to inhibit the replication of certain mammalian DNA viruses as well as RNA viruses. In this study, we unveil RFP as a potent inhibitor of PRRSV both in Marc-145 cells (half-maximal inhibitory concentration 61.26 µM) and porcine alveolar macrophages (half-maximal inhibitory concentration 53.09 µM). The inhibitory effect of RFP occurred during viral replication rather than binding, internalization and release. We also demonstrated that RFP inhibits PRRSV proteins production in the early stage of infection, without inhibiting host protein synthesis. Moreover, RFP effectively restricted porcine epidemic diarrhea virus (PEDV) and porcine enteric alphacoronavirus (PEAV) infection in Vero cells. In summary, these findings indicate the promising potential of RFP as a therapeutic agent for PRRSV, PEDV and PEAV infection in pig farms. [ABSTRACT FROM AUTHOR]

Coronaviruses employ various strategies for survival, among which the activation of endogenous or exogenous apoptosis stands out, with viral proteins playing a pivotal role. Notably, highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV exhibit a greater array of non-structural proteins compared to low-pathogenic strains, facilitating their ability to induce apoptosis via multiple pathways. Moreover, these viral proteins are adept at dampening host immune responses, thereby bolstering viral replication and persistence. This review delves into the intricate interplay between highly pathogenic coronaviruses and apoptosis, systematically elucidating the molecular mechanisms underpinning apoptosis induction by viral proteins. Furthermore, it explores the potential therapeutic avenues stemming from apoptosis inhibition as antiviral agents and the utilization of apoptosis-inducing viral proteins as therapeutic modalities. These insights not only shed light on viral pathogenesis but also offer novel perspectives for cancer therapy. Highlights: • Apoptosis plays an important role in the pathogenesis of the highly pathogenic coronavirus • The structural and non-structural proteins of highly pathogenic coronaviruses exert significant influence over apoptosis regulation • Apoptosis inhibitors exhibits promising antiviral effects, thereby presenting a potential avenue for the development of novel therapeutics targeting COVID-19. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 (COVID-19), a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related sickness that has already claimed millions of lives throughout the world, is one of the most contagious illnesses in known human history. At this time, neither vaccines nor effective medicines exist that can effectively cure COVID-19 patients or stop the virus from spreading. Even though the creation of drugs and vaccines may take a while, scientific communities all over the world have reacted rapidly and have been working ceaselessly on them. In light of this uncertainty, repurposing currently existing antiviral drugs may be the best line of action to speed the creation of effective SARS-CoV-2 therapeutics. Updated information is also required on potential pharmacological targets, therapeutic and vaccine development, and results. In this study, we propose topological descriptors and status distance-based polynomials for many COVID-19 antiviral drugs. The quantitative structure–property relationship (QSPR) connection of the proposed topological indices (TIs) is also investigated. Curve fitting models are obtained and looked at for the physico-chemical properties of the COVID-19 drugs in line with the specified indices. Our models and results may contribute to the identification of innovative therapeutics for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

The possible impact of antivirals on ecosystems and the emergence of antiviral resistance are the reasons for concern about their environmental release. Consequently, there has been a significant increase in curiosity regarding their presence in both organic and synthetic systems in recent years. The primary objective of this review is to address the void of information regarding the global presence of antiviral drugs in both wastewater and natural water sources. Photocatalytic degradation of pollutants is an eco-friendly, cost-effective method that effectively addresses environmental degradation. The development of efficient photocatalysts remains a significant issue in accelerating the degradation of pollutants, especially when employing solar light. Thus, the development of Z-scheme and S-scheme semiconductor heterojunctions has emerged as a viable method to improve light absorption and enhance the redox capability of photocatalysts. The principles of Z-scheme and S-scheme are reviewed extensively. The degradation route and occurrence of antiviral are discussed briefly. Finally, a short preview of the degradation of antiviral using Z-scheme and S-scheme is also highlighted. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic continues to pose significant challenges worldwide, despite widespread vaccination. Researchers are actively exploring antiviral treatments to assess their efficacy against emerging virus variants. The aim of the study is to employ M-polynomial, neighborhood M-polynomial approach and QSPR/QSAR analysis to evaluate specific antiviral drugs including Lopinavir, Ritonavir, Arbidol, Thalidomide, Chloroquine, Hydroxychloroquine, Theaflavin and Remdesivir. Utilizing degree-based and neighborhood degree sum-based topological indices on molecular multigraphs reveals insights into the physicochemical properties of these drugs, such as polar surface area, polarizability, surface tension, boiling point, enthalpy of vaporization, flash point, molar refraction and molar volume are crucial in predicting their efficacy against viruses. These properties influence the solubility, permeability, and bio availability of the drugs, which in turn affect their ability to interact with viral targets and inhibit viral replication. In QSPR analysis, molecular multigraphs yield notable correlation coefficients exceeding those from simple graphs: molar refraction (MR) (0.9860), polarizability (P) (0.9861), surface tension (ST) (0.6086), molar volume (MV) (0.9353) using degree-based indices, and flash point (FP) (0.9781), surface tension (ST) (0.7841) using neighborhood degree sum-based indices. QSAR models, constructed through multiple linear regressions (MLR) with a backward elimination approach at a significance level of 0.05, exhibit promising predictive capabilities highlighting the significance of the biological activity I C 50 (Half maximal inhibitory concentration). Notably, the alignment of predicted and observed values for Remdesivir's with obs p I C 50 = 6.01 ,pred p I C 50 = 6.01 ( p I C 50 represents the negative logarithm of I C 50 ) underscores the accuracy of multigraph-based QSAR analysis. The primary objective is to showcase the valuable contribution of multigraphs to QSPR and QSAR analyses, offering crucial insights into molecular structures and antiviral properties. The integration of physicochemical applications enhances our understanding of factors influencing antiviral drug efficacy, essential for combating emerging viral strains effectively. [ABSTRACT FROM AUTHOR]

Background: The global prevalence of hepatitis B virus (HBV) has presented a persistent challenge for public health prevention and treatment. However, studies that assess the public's access to anti-HBV drugs are absent. Aim: To examine the availability, pricing, and affordability of anti-HBV drugs in Jiangsu province, China and provide recommendations for improvement. Method: An enhanced methodology developed by the World Health Organization (WHO) and Health Action International was applied in a cross-sectional study that included 1026 healthcare facilities distributed in 13 prefectural-level cities in Jiangsu province. Results: Since almost all drugs had an availability of less than 30%, the accessibility of anti-HBV drugs was notably low. Primary healthcare facilities had the lowest availability, reporting 1.4% for Original Brands (OBs) and 1.7% for lowest-priced generics (LPGs). Furthermore, the northern Jiangsu region recorded the lowest availability at 0.7%. LPGs demonstrated higher availability than OBs, with median availability probabilities of 2.6% and 1.4%, respectively. The drugs listed on the WHO Essential Medicines List exhibited higher availability than those on other lists. The median price ratios for OBs, LPGs, and volume-based purchasing drugs were 0.83, 0.50, and 0.27, respectively, less than 1.5 times the international reference price. Despite favorable pricing, affordability rate was 23% for urban residents and 0% for rural residents, which was discouraging. Conclusion: Low availability and affordability of anti-HBV drugs were observed. Policy recommendations should emphasize the improvement of LPG availability by incentivizing priority prescribing. Healthcare subsidies should be provided more effectively and equitably. [ABSTRACT FROM AUTHOR]

Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56 years), serum creatinine 127 (101–153) µmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1–3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15–22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106–159) µmol/L post-COVID-19 infection and 128 (101–161) µmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2, SARS2) is responsible for the COVID-19 pandemic and infections that continue to affect the lives of millions of people worldwide, especially those who are older and/or immunocompromised. The SARS2 main protease enzyme, Mpro (also called 3C-like protease, 3CLpro), is a bona fide drug target as evidenced by potent inhibition with nirmatrelvir and ensitrelvir, the active components of the drugs Paxlovid and Xocova, respectively. However, the existence of nirmatrelvir and ensitrelvir-resistant isolates underscores the need to develop next-generation drugs with different resistance profiles and/or distinct mechanisms of action. Here, we report the results of a high-throughput screen of 649,568 compounds using a cellular gain-of-signal assay. In this assay, Mpro inhibits expression of a luciferase reporter, and 8,777 small molecules were considered hits by causing a gain in luciferase activity 3x SD above the sample field activity (6.8% gain-of-signal relative to 100 µM GC376). Single concentration and dose-response gain-of-signal experiments confirmed 3,522/8,762 compounds as candidate inhibitors. In parallel, all initial high-throughput screening hits were tested in a peptide cleavage assay with purified Mpro and only 39/8,762 showed inhibition. Importantly, 19/39 compounds (49%) re-tested positive in both SARS2 assays, including two previously reported Mpro inhibitors, demonstrating the efficacy of the overall screening strategy. This approach led to the rediscovery of known Mpro inhibitors such as calpain inhibitor II, as well as to the discovery of novel compounds that provide chemical information for future drug development efforts.

The ban of antiviral drugs in food-producing animals in several parts of the world, latest by Commission Delegated Regulation (EU) 2022/1644, has increased the need for food control laboratories to develop analytical methods and perform official controls. However, little is known about antiviral drugs, their use, and its analysis in food-producing animals in the EU. This review aims to provide insights into relevant viruses, antiviral drugs, and animal-derived matrices for analytical method development and monitoring purposes to implement in food control laboratories. For years, animal viruses, such as African swine fever and avian influenza, have caused many outbreaks. Besides, they led to large economic losses due to the applied control measures and a lack of available treatments. Considering these losses and the known effectiveness of authorized human antiviral drugs in different organisms, medicines such as amantadine in Chinese poultry have been misused. Various analytical methods, including screening assays and sensors (published 2016–2023), and mass spectrometry methods (published 2012–2023) have been outlined in this review for the monitoring of antiviral drugs in animal-derived matrices. However, pharmacokinetics information on metabolite formation and distribution of these substances in different animal-derived matrices is incomplete. Additionally, apart from a few countries, there is a lack of available data on the potential misuse of different antiviral drugs in animal-derived matrices. Although a handful of important antiviral drugs, such as influenza, broad-spectrum, antiretroviral, and herpes drugs, and animal-derived matrices, such as chicken muscle, are identified, the priority of the scope should be further specified by closing the aforementioned gaps.

الملخص: أهداف البحث: ينتمي فيروس غرب النيل إلى فصيلة الفيروسات المصفرة ويسبب حمى النيل الغربي، وآلية انتقاله تكون عن طريق نوع بعوض الكيولكس. الضحايا في الغالب لا تظهر عليهم أعراض، والقليل منهم يظهر عليهم الأعراض الشائعة، 10٪ من الخلايا العصبية التي يسببها هذا الفيروس سوف تسبب الوفاة. ومع ذلك، حتى الآن لا تزال البروتينات المشفرة بواسطة هذه الجينات غير مميزة، وفي هذا الصدد، فإن فهم وظائف وبنية هذه البروتينات له أهمية في صياغة الأدوية المضادة للفيروسات. طريقة البحث: في الدراسة البحثية الحالية، تم استخدام منهجية ''ان-سيليكو'' مثل مجموعة متنوعة من أدوات المعلومات الحيوية وقواعد البيانات المستخدمة لتحليل بروتينات بروتينات فيروس غرب النيل بشكل فردي، والخصائص الفيزيائية والكيميائية، واكتشاف المجالات المحفوظة، وتحديد المناطق القابلة للذوبان وعبر الغشاء، وتوطين الإشارة، واضطراب البروتين وخصائص البنية الثانوية وهياكل البروتين ثلاثية الأبعاد الخاصة بكل منها. النتائج: من بين أحد عشر بروتينا، ثمانية بروتينات أعلى من خمسين بالمائة من محتوى ''جي سي''، وثمانية بروتينات ذات قيم ''بي إل'' الأساسية، وثلاثة بروتينات غير مستقرة في الظروف المختبرية، وأربعة بروتينات ذات قيمة ''ايه آي'' أعلى من 100 قابلة للحرارة، وبعض البروتينات ذات قيم ''جرافي'' سلبية من التحليل الفيزيائي والكيميائي . تتم مشاركة جميع المجالات المحفوظة بالبروتين مع عائلة الفيروسات المصفرة. خمسة بروتينات قابلة للذوبان ولا تحتوي على مناطق غشائية. يشير بروتينان إلى توطين الشبكة الإندوبلازمية المضيفة. أظهر غير الهيكلي 2أ (إن إس) اضطرابا منخفضا في البروتين. تمثل السمات الهيكلية الثانوية وبيانات نماذج البنية الثالثة مصدرا كيميائيا حيويا قيما يوفر جزءا من المعلومات القوية لتصميم ركائز انتقائية ومثبطات اصطناعية. الاستنتاجات: يمكن استخدام بروتينات فيروس غرب النيل ''إن إس 2أ'' و ''إن إس 2ب'' و ''بي إم'' و ''إن إس 3'' و ''إن إس 5'' كأهداف دوائية للدراسة الدوائية لتصميم مركبات الرصاص المضادة للفيروسات. Abstract: Objectives: West Nile virus (WNV) belongs to the Flaviviridae family and causes West Nile fever. The mechanism of transmission involves the culex mosquito species. Infected individuals are primarily asymptomatic, and few exhibit common symptoms. Moreover, 10 % of neuronal infection caused by this virus cause death. The proteins encoded by these genes had been uncharacterized, although understanding their function and structure is important for formulating antiviral drugs. Methods: Herein, we used in silico approaches, including various bioinformatic tools and databases, to analyse the proteins from the WNV polyprotein individually. The characterization included GC content, physicochemical properties, conserved domains, soluble and transmembrane regions, signal localization, protein disorder, and secondary structure features and their respective 3D protein structures. Results: Among 11 proteins, eight had >50 % GC content, eight proteins had basic pI values, three proteins were unstable under in vitro conditions, four were thermostable according to >100 AI values and some had negative GRAVY values in physicochemical analyses. All protein-conserved domains were shared among Flaviviridae family members. Five proteins were soluble and lacked transmembrane regions. Two proteins had signals for localization in the host endoplasmic reticulum. Non-structural (NS) 2A showed low protein disorder. The secondary structural features and tertiary structure models provide a valuable biochemical resource for designing selective substrates and synthetic inhibitors. Conclusions: WNV proteins NS2A, NS2B, PM, NS3 and NS5 can be used as drug targets for the pharmacological design of lead antiviral compounds.

Sandra Megantara,1,2 Agus Rusdin,3 Arif Budiman,3 Shaharum Shamsuddin,4 Noratiqah Mohtar,5 Muchtaridi Muchtaridi1,2,6 1Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 2Research Collaboration Centre for Theranostic Radio Pharmaceuticals, National Research and Innovation Agency (BRIN), Sumedang, 45363, Indonesia; 3Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 4School of Health, Universiti Sains Malaysia, Penang, 11800, Malaysia; 5School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800, Malaysia; 6Functional Nano Powder University Center of Excellence (FiNder U CoE), Universitas Padjadjaran, Sumedang, 45363, IndonesiaCorrespondence: Sandra Megantara, Tel +62-813-2066-3583, Email s.megantara@unpad.ac.idAbstract: Since the beginning of the coronavirus pandemic in late 2019, viral infections have become one of the top three causes of mortality worldwide. Immunization and the use of immunomodulatory drugs are effective ways to prevent and treat viral infections. However, the primary therapy for managing viral infections remains antiviral and antiretroviral medication. Unfortunately, these drugs are often limited by physicochemical constraints such as low target selectivity and poor aqueous solubility. Although several modifications have been made to enhance the physicochemical characteristics and efficacy of these drugs, there are few published studies that summarize and compare these modifications. Our review systematically synthesized and discussed antiviral drug modification reports from publications indexed in Scopus, PubMed, and Google Scholar databases. We examined various approaches that were investigated to address physicochemical issues and increase activity, including liposomes, cocrystals, solid dispersions, salt modifications, and nanoparticle drug delivery systems. We were impressed by how well each strategy addressed physicochemical issues and improved antiviral activity. In conclusion, these modifications represent a promising way to improve the physicochemical characteristics, functionality, and effectiveness of antivirals in clinical therapy.Keywords: antiviral drugs, current modifications, drug delivery system, physicochemical properties

Abstract Lumpy skin disease virus (LSDV) infection is a major socio-economic issue that seriously threatens the global cattle-farming industry. Here, a recombinant virus LSDV-ΔTK/EGFP, expressing enhanced green fluorescent protein (EGFP), was constructed with a homologous recombination system and applied to the high-throughput screening of antiviral drugs. LSDV-ΔTK/EGFP replicates in various kidney cell lines, consistent with wild-type LSDV. The cytopathic effect, viral particle morphology, and growth performance of LSDV-ΔTK/EGFP are consistent with those of wild-type LSDV. High-throughput screening allowed to identify several molecules that inhibit LSDV-ΔTK/EGFP replication. The strong inhibitory effect of theaflavin on LSDV was identified when 100 antiviral drugs were screened in vitro. An infection time analysis showed that theaflavin plays a role in the entry of LSDV into cells and in subsequent viral replication stages. The development of this recombinant virus will contribute to the development of LSDV-directed antiviral drugs and the study of viral replication and mechanisms of action.

Background Coronavirus disease 2019 (COVID-19) has created the need to evaluate drugs such as favipiravir (FPV), an antiviral inhibitor of RNA-dependent RNA-polymerase (RdRp), and Maraviroc (MVC), an antiretroviral that antagonizes the chemokine receptor CCR5, which could affect the modulation of inflammation and viral replication in the treatment of COVID-19. We sought to evaluate the effect of MVC and/or FPV plus systemic steroid (SS) vs. SS alone on the viral load and progression to critical disease. Methods Sixteen patients with severe COVID-19 were evaluated in three treatment arms: 1) SS only (n=6), 2) SS plus one test drug MVC or FPV (n=5), and 3) SS plus both test drugs (MVC and FPV, n=5). The viral load was determined for N, E, and RdRp viral genes. Results A significant decrease in viral load was observed in the three treatment groups, with a larger effect size in the group that combined SS with both test drugs. The E, N, and RdRp genes with Cohen’s d were 120%, 123%, and 50%, respectively. Conclusions The largest effect on viral load reduction, as measured by effect size, was observed in the combination treatment group; however, no statistical significance was found, and it did not prevent progression to critical illness.

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.

Viruses are a real threat to every organism at any stage of life leading to extensive infections and casualties. N-heterocycles can affect the viral life cycle at many points, including viral entrance into host cells, viral genome replication, and the production of novel viral species. Certain N-heterocycles can also stimulate the host's immune system, producing antiviral cytokines and chemokines that can stop the reproduction of viruses. This review focused on recent five- or six-membered synthetic N-heterocyclic molecules showing antiviral activity through SAR analyses. The review will assist in identifying robust scaffolds that might be utilized to create effective antiviral drugs with either no or few side effects. [ABSTRACT FROM AUTHOR]

Several opportunities to investigate a variety of treatment techniques for the prevention of infection have arisen as a result of the unprecedented COVID-19 pandemic. The development of vaccinations against the coronavirus has been the focus of the efforts of a large number of researchers worldwide. It has been of utmost importance to administer treatment adequately for the illness while searching for suitable antiviral medications. This study aims to investigate the numerous causes of infections and the various treatments in use. Furthermore, it aims to create therapeutic and preventive options derived from plants that can be employed in conjunction with COVID-19 therapy. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Eurasian Journal of Ecology is the property of Al-Farabi Kazakh National University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bovine parainfluenza virus type 3 (BPIV3) is a key pathogen associated with bovine respiratory disease complex (BRDC). However, its specific pathogenesis mechanisms have not been fully elucidated. Reverse genetics provides a useful method for understanding the pathogenic mechanism of BPIV3. To ensure the functionality of the rescue platforms, we first constructed a minigenome (MG) system of BPIV3 utilizing a 5-plasmid system in this investigation. Then, a full-length infection clone of BPIV3 was obtained from the SX-2021 strain, and different methods were employed to identify the rescued virus. Additionally, we recovered a recombinant BPIV3 using the reverse genetics system that could express enhanced green fluorescence protein (eGFP). Through the growth curve assays, the replicate capability of rBPIV3-SX-EGFP was found to be similar to that of the parental virus. Subsequently, the rBPIV3-SX-EGFP was used to determine the antiviral activity of ribavirin. The results showed that ribavirin had an anti-BPIV3 effect in MDBK cells. In conclusion, the successful development of a reverse genetic system for the SX-2021 strain establishes a foundation for future studies on BPIV3, including investigations into its pathogenic mechanism, gene function, and antiviral screening properties. [ABSTRACT FROM AUTHOR]

Lumpy skin disease virus (LSDV) infection is a major socio-economic issue that seriously threatens the global cattle-farming industry. Here, a recombinant virus LSDV-ΔTK/EGFP, expressing enhanced green fluorescent protein (EGFP), was constructed with a homologous recombination system and applied to the high-throughput screening of antiviral drugs. LSDV-ΔTK/EGFP replicates in various kidney cell lines, consistent with wild-type LSDV. The cytopathic effect, viral particle morphology, and growth performance of LSDV-ΔTK/EGFP are consistent with those of wild-type LSDV. High-throughput screening allowed to identify several molecules that inhibit LSDV-ΔTK/EGFP replication. The strong inhibitory effect of theaflavin on LSDV was identified when 100 antiviral drugs were screened in vitro. An infection time analysis showed that theaflavin plays a role in the entry of LSDV into cells and in subsequent viral replication stages. The development of this recombinant virus will contribute to the development of LSDV-directed antiviral drugs and the study of viral replication and mechanisms of action. [ABSTRACT FROM AUTHOR]

Pseudorabies is an acute and febrile infectious disease caused by pseudorabies virus (PRV), a member of the family Herpesviridae. Currently, PRV is predominantly endemoepidemic and has caused significant economic losses among domestic pigs. Other animals have been proven to be susceptible to PRV, with a mortality rate of 100%. In addition, 30 human cases of PRV infection have been reported in China since 2017, and all patients have shown severe neurological symptoms and eventually died or developed various neurological sequelae. In these cases, broad-spectrum anti-herpesvirus drugs and integrated treatments were mostly applied. However, the inhibitory effect of the commonly used anti-herpesvirus drugs (e.g., acyclovir, etc.) against PRV were evaluated and found to be limited in this study. It is therefore urgent and important to develop drugs that are clinically effective against PRV infection. Here, we constructed a high-throughput method for screening antiviral drugs based on fluorescence-tagged PRV strains and multi-modal microplate readers that detect fluorescence intensity to account for virus proliferation. A total of 2104 small molecule drugs approved by the U.S. Food and Drug Administration (FDA) were studied and validated by applying this screening model, and 104 drugs providing more than 75% inhibition of fluorescence intensity were selected. Furthermore, 10 drugs that could significantly inhibit PRV proliferation in vitro were strictly identified based on their cytopathic effects, virus titer, and viral gene expression, etc. Based on the determined 50% cytotoxic concentration (CC50) and 50% inhibitory concentration (IC50), the selectivity index (SI) was calculated to be 26.3–3937.2 for these 10 drugs, indicating excellent drugability. The antiviral effects of the 10 drugs were then assessed in a mouse model. It was found that 10 mg/kg brincidofovir administered continuously for 5 days provided 100% protection in mice challenged with lethal doses of the human-origin PRV strain hSD-1/2019. Brincidofovir significantly attenuated symptoms and pathological changes in infected mice. Additionally, time-of-addition experiments confirmed that brincidofovir inhibited the proliferation of PRV mainly by interfering with the viral replication stage. Therefore, this study confirms that brincidofovir can significantly inhibit PRV both in vitro and in vivo and is expected to be an effective drug candidate for the clinical treatment of PRV infections. [ABSTRACT FROM AUTHOR]

Avian influenza viruses (AIVs) have posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics. [ABSTRACT FROM AUTHOR]

The Zika virus (ZIKV) is a mosquito-borne virus that already poses a danger to worldwide human health. Patients infected with ZIKV generally have mild symptoms like a low-grade fever and joint pain. However, severe symptoms can also occur, such as Guillain-Barré syndrome, neuropathy, and myelitis. Pregnant women infected with ZIKV may also cause microcephaly in newborns. To date, we still lack conventional antiviral drugs to treat ZIKV infections. Marine natural products have novel structures and diverse biological activities. They have been discovered to have antibacterial, antiviral, anticancer, and other therapeutic effects. Therefore, marine products are important resources for compounds for innovative medicines. In this study, we identified a marine natural product, harzianopyridone (HAR), that could inhibit ZIKV replication with EC50 values from 0.46 to 2.63 µM while not showing obvious cytotoxicity in multiple cellular models (CC50 > 45 µM). Further, it also reduced the expression of viral proteins and protected cells from viral infection. More importantly, we found that HAR directly bound to the ZIKV RNA-dependent RNA polymerase (RdRp) and suppressed its polymerase activity. Collectively, our findings provide HAR as an option for the development of anti-ZIKV drugs. [ABSTRACT FROM AUTHOR]

In the present study, the multiple ligands simultaneous docking technique was employed to explore the feasibility of developing the protein-based nanocarriers in which the therapeutic agents (antiviral drugs) will be combined with a visualizing agent (the phosphonium dye TDV). By varying both the protein (serum albumin, lyso-zyme, cytochrome c, insulin) and antiviral agent (favipiravir, molnupiravir, nirmatrelvir, ritonavir) components of the examined complexes it was demonstrated that in the albumin- and cytochrome c-containing systems the TDV and antiviral dyes occupy distinct binding sites on the protein molecule, exhibiting no interference with each other. It was found that the TDV propensity to reside within the same insulin cavity as the antiviral agent might hinder the drug's release from the nanocarrier. Our results indicate that the most promising energetically stable protein-drug-TDV systems for developing protein-based nanocarriers with the examined antiviral drugs can be created on a basis of serum albumin. [ABSTRACT FROM AUTHOR]

Antibiotics treat bacterial infections, whereas antiviral drugs treat viral illnesses. Antivirals are used to treat a variety of infectious diseases, including COVID-19 and influenza. The technique of reversed-phase high-performance liquid chromatography (RP-HPLC) provides more sensitivity and precision than other approaches, particularly spectrophotometric. This research seeks to develop a simple method for simultaneously quantifying acyclovir, amantadine, and oseltamivir in creams and capsules. The RP-HPLC method optimization and development for verifying the separation and quantification of three antiviral drugs included the investigation of the optimal buffer concentration, pH value, and acetonitrile content. On a C8 HyperClone BDS column, the RP-HPLC system with UV detection achieved separation (250 x 4.60 mm, 130A, and 5). The mixture of acetonitrile and acetate buffer as mobile phase gradient elution at a detection wavelength of 254 nm and 1 mL/min flow rate. The proposed method provided a linear range of 0.08-10.5, 0.06-4.5 and 0.02-14 μg/mL, as well as excellent validated values for LOD (0.0205, 0.0107, and 0.0083 μg/mL) and LOQ (0.0621, 0.0324 and 0.0251 μg/mL) with a coefficient of determination (r2) of the regression line of 0.9998, 0.9988, and 0.9994 for acyclovir, amantadine, and oseltamivir, respectively. [ABSTRACT FROM AUTHOR]