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With more than 23 million infections and more than 814,000 deaths worldwide, the coronavirus disease-2019 (COVID-19) pandemic is still far from over. Several classes of drugs including antivirals, antiretrovirals, anti-inflammatory, immunomodulatory, and antibiotics have been tried with varying levels of success. Still, there is lack of any specific therapy to deal with this infection. Although less than 30% of these patients require intensive care unit admission, morbidity and mortality in this subgroup of patients remain high. Hence, it becomes imperative to have general principles to guide intensivists managing these patients. However, as the literature emerges, these recommendations may change and hence, frequent updates may be required. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has resulted in millions of fatalities worldwide. The case of pediatric cancer patients stands out since, despite being considered a population at risk, few studies have been carried out concerning symptom detection or the description of the mechanisms capable of modifying the course of the COVID-19 disease, such as the interaction and response between the virus and the treatment given to cancer patients. By synthesizing existing studies, this paper aims to expose the treatment challenges for pediatric patients with COVID-19 in an oncology context. Additionally, this updated review includes studies that utilized the antiviral agents Remdesivir and PaxlovidTM in pediatric cancer patients. There is no specific treatment designed exclusively for pediatric cancer patients dealing with COVID-19, and it is advisable to avoid self-medication to prevent potential side effects. Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Analysis of the physical-chemical characteristics of chemical structures requires the incorporation of topological indices into account. A structure-based approach that concentrates antiviral treatment on the main protease of the SARS-COV-2 virus. One degree-based measure that is a little comparable to the Zagreb index and Lanzhou index. This paper analyzed the effectiveness of the chemical compounds pyroxene, amphibole, detour-saturated plants, and several antiviral medications listed for the Lanzhou index. The obtained results demonstrate a significant relationship between the Lanzhou index under investigation and the physicochemical features of potential antiviral medications. The Lanzhou index for antioxidant drugs for M polynomial is enumerated. [ABSTRACT FROM AUTHOR]

Objectives : In light of the ongoing global pandemic, this paper reviews data on a number of potential and approved agents for COVID-19 disease management, including corticosteroids, remdesivir, tocilizumab, and monoclonal antibody combinations. Dose considerations, potential drug–drug interactions, and access issues are discussed. Key findings : Remdesivir is the first antiviral agent approved for the treatment of COVID-19, based on results from large clinical trials showing reduction in recovery time, faster clinical improvement, and decrease in time to discharge with remdesivir. Dexamethasone and tocilizumab have demonstrated mortality benefits in large, randomized controlled trials. Consequently, the use of corticosteroids has become the standard of care for hospitalized patients with severe or critical COVID-19, while tocilizumab is recommended for use in combination with a corticosteroid in certain hospitalized patients. Recently, monoclonal antibody combinations bamlanivimab/etesevimab and casirivimab/imdevimab received emergency use authorizations for use in non-hospitalized patients with mild-to-moderate COVID-19 at high risk of disease progression. Summary : As data from large clinical trials emerge, the paradigm of COVID-19 treatments has shifted significantly. The use of corticosteroids, remdesivir, and tocilizumab depend on disease severity. Emerging data on monoclonal antibody combinations are promising, but further data are required. Pharmacists can play a role in ensuring appropriate access, correct administration, and safe use of COVID-19 treatments and are encouraged to stay abreast of new developments. [ABSTRACT FROM AUTHOR]

BACKGROUND: The pandemic caused by the novel coronavirus disease (COVID-19) since early 2020 is one of the most significant global health issues in history. Although there is currently no specific treatment for COVID-19, researchers have provided a whole array of potential treatments, both from the Western medicine approach, which is molecular target and pathogenesis based, and from the traditional Chinese medicine (TCM) approach, which is based on the exposure to toxins/pathogens and the balance of the body to combat them for recovery. OBJECTIVE: The aim of this research is to find combinations of Western medicine and TCM that may offer better therapeutic efficacy synergystically with a better adverse events profile. The findings of the research may provide a new insight in the development of the treatment of COVID-19. METHODS: From the Western medicine perspective, drugs target the mechanisms of viral infection, including the stages of viral entry (Arbidol, Camostat Mesylate, Convalescent Plasma therapy) and viral replication (Lopinavir/Ritonavir, Redemsivir, Ribavirin). Additional therapies target host defenses, preventing cytokine storms (Tocilizumab) and stimulating the immune system (Interferons). On the other hand, TCM also proposed a number of treatment methods for COVID-19 with new scientific approaches identifying their antiviral and immunomodulatory activities. The novel combination of Western medicine and TCM can be proposed by analyzing their respective molecular targets. RESULTS: Although TCM is not generally accepted in the Western community because of the general lack of knowledge on their detailed mechanisms, studies and clinical trials suggest that TCM could be beneficial in combating COVID-19. CONCLUSION: Based on the principle of combining TCM and Western medicine, two combinations are tested effective in clinical trials, and three possible combinations that might be effective are proposed in the paper. [ABSTRACT FROM AUTHOR]

Simple Summary: This article regards the incidence of long COVID symptoms in a cohort of patients with cancer with or without previous treatment with early therapies anti-SARS-CoV-2 in an out-of-hospital setting. The enrolled patients were invited to take part in the survey by telephone at least 12 weeks after COVID-19 diagnosis in order to evaluate the incidence of long COVID symptoms. To date, no papers have focused on the oncological population managed at home with the early anti-SARS-CoV-2 therapies. The overlap between the symptoms related to the oncological disease/oncological treatment and the symptoms of long COVID is one of the main future challenges that oncologists will have to manage. The incidence of long COVID in a cohort of patients with cancer with or without previous treatment with early therapies anti-SARS-CoV-2 in an out-of-hospital setting have to be elucidated. We prospectively enrolled all patients treated for a solid tumor at the department of Medical Oncology of the Fondazione IRCCS Policlinico San Matteo with a positive SARS-CoV-2 antigen or polymerase chain reaction test from January to September 2022 (Omicron surge). Ninety-seven patients answered the survey questions by telephone at least 12 weeks after COVID-19 diagnosis in order to evaluate the incidence of long COVID symptoms. Only twelve patients (12.4%) reported long COVID. No significant difference between early therapies anti-SARS-CoV-2 31 and long COVID (p = 0.443) was seen. The female sex (p = 0.024) and diabetes mellitus (p = 0.014) are significantly associated with long COVID. No statistically significant difference between the two groups (Long COVID vs. No Long COVID) according to the time to nasal swab viral clearance (p = 0.078). The overlap between the symptoms related to the oncological disease/oncological treatment and the symptoms of long COVID is one of the main future challenges that oncologists will have to manage. [ABSTRACT FROM AUTHOR]

Remdesivir (RDV) is the only antiviral drug approved for COVID-19 therapy by the FDA. Another drug LAGEVRIO™ (molnupiravir) though has not been approved yet by FDA but has been authorized on December 23, 2021, for emergency use to treat adults with mild-to moderate COVID-19 symptoms and for whom alternative COVID-19 treatment options are not clinically appropriate. The fact is that the efficacy of RDV is, however, limited in vivo though it is highly promising in vitro against SARS-CoV-2 virus. In this paper we are focusing on the action mechanism of RDV and how it can be improved in vivo. The stability of RDV alone and on encapsulation with our platform technology based polymer NV-387 (NV-CoV-2), were compared in presence of plasma in vitro and in vivo. Furthermore, a non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV CoV-2 (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats was done. In addition, the antiviral activity of NV-CoV-2 and NV-CoV-2-R was compared with RDV in a cell culture study. The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma-mediated catabolism in both in vitro and in vivo, studies; (ii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2 and NV-CoV-2-R) showed no toxic effects. (iii) Body weight measurements and survival rates of the NL-63 infected rats were similar to the uninfected rats after treatment with NV-CoV-2 and NV-CoV-2-R. Overall, the efficacy as an antiviral regimens were found in this order as below; NV-CoV-2-R > NV-CoV-2 > RDV. Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect against different variants of the coronaviruses. First, NV-CoV-2 is an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit. All together, NV-CoV-2-R is the safest and efficient regimen against COVID-19. [ABSTRACT FROM AUTHOR]

Despite intramuscular vaccines saving millions of lives, constant devastating waves of SARS-CoV-2 infections continue. The elimination of COVID-19 is challenging, but necessary in order to avoid millions more people who would suffer from long COVID if we fail. Our paper describes rapidly advancing and innovative therapeutic strategies for the early stage of infection with COVID-19 so that tolerating continuing cycles of infection should be unnecessary in the future. These therapies include new vaccines with broader specificities, nasal therapies and antiviral drugs some targeting COVID-19 at the first stage of infection and preventing the virus entering the body in the first place. Our article describes the advantages and disadvantages of each of these therapeutic options which in various combinations could eventually prevent renewed waves of infection. Finally, important consideration is given to political, social and economic barriers that since 2020 hindered vaccine application and are likely to interfere again with any COVID-19 endgame. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has impacted the lives and wellbeing of many people. This globally widespread disease poses a significant public health concern that urges to discover an effective treatment. This review paper discusses the effectiveness of repurposed drugs used to treat COVID-19 and potential novel therapies for COVID-19. Among the various repurposed drugs, remdesivir is the only agent approved by the Food and Drug Administration (FDA) to treat COVID-19. On the other hand, several drugs have been listed in the Emergency Use Authorization (EUA) by the FDA to treat COVID-19, including casirivimab and imdevimab, baricitinib (in combination with remdesivir), bamlanivimab, tocilizumab, and IL-6 inhibitors. In addition, in vitro and clinical studies have suggested cepharanthine, sotrovimab, and XAV-19 as potential treatments to manage COVID-19. Due to inadequate understanding of COVID-19 and the rapid mutation of SARS-CoV-2, COVID-19 remains a threat to global public health, with vaccination considered the most effective method to decrease COVID-19 transmission currently. Nevertheless, with the intense efforts of clinical researchers globally, more promising treatments for COVID-19 will be established in the future. [ABSTRACT FROM AUTHOR]

The corona virus disease 2019 (COVID-19) pandemic, which originated in the city of Wuhan, China, has rapidly spread to various countries, with many cases having been reported. Some existing antiviral agents showed positive results to inhibit the infection and transmission of the novel corona virus 2019 (2019-nCoV) in vitro. Covaxin is India's first indigenous COVID-19 vaccine. In this paper, we introduce the Gourava and hyper-Gourava polynomials of a graph. We compute the Gourava and hyper-Gourava polynomials of some specific class of graphs. Further, we obtain the Gourava and hyper-Gourava polynomials of some chemical structures viz., chloroquine, hydroxychloroquine, remdesivir and theaflavin which were used in the treatment of COVID-19. The Gourava and hyper-Gourava indices are investigated for the aforesaid antiviral drugs using polynomial approach. The Indian Council of Medical Research and Bharat Biotech announced that Phase 3 results of covaxin, developed by them, have shown an interim vaccine efficacy of 81 percent. So, the results obtained may be useful for finding the design of new medicine for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

The ongoing global development of the COVID-19 epidemic has led to in-depth research on the disease, including therapeutic agents. As a promising specific antiviral agents, the neutralizing antibodies have been successfully applied on some viral infectious diseases. Currently, the development of neutralizing antibodies against SARS-CoV-2 is progressing rapidly internationally, several antibodies have been authorized for emergency use. This paper reviews the effect targets of neutralizing antibodies against SARS-CoV-2, the research progress of drugs, and the problems and shortcomings that need attention. [ABSTRACT FROM AUTHOR]

The main objective of the current systematic review was to report the antiviral and anti-inflammatory effects of bioactive molecules class known as alkaloids against SARS-COV-2 disease. These bioactive compounds were characterized by their potential replication inhibitory ability by DNA intercalating effect, and might be powerful agents against infections caused by several viruses, therefore it can be a viable strategy for COVID-19 management. PubMed, ScienceDirect, Google Scholar and SpringerLink, databases have been chosen to look for keywords like DNA intercalators, alkaloids, antiviral activity, anti-inflammatory effect, coronavirus, SARS-CoV-2. Two reviewers have evaluated the quality of 60 articles extracted from the four databases till 15th of May 2021, using inclusions and exclusions criteria, 25 papers were accepted and treated in this systematic review, performed based on PRISMA protocol. Results disclosed that alkaloids have key roles in viral replication inhibition, quinine and emetine showed a noticeable therapeutic effect against SARS-COV-2 virus, however emetine revealed modifications in the electrocardiogram (ECG), unlike sanguinarine and berberine that showed low human toxicity. Tetrandrine, fangchinoline and cepharantine could be classified as remedies in case of Coronavirus ailment. Chelidonine, coptisine, skimmianine, protropine, palmatine, cinchonine, harmine and dictamine represented important agents for clinical researches or as precursors for antiviral drug's formulation. [ABSTRACT FROM AUTHOR]

Sulfated polysaccharides and other polyanions have been promising candidates in antiviral research for decades. These substances gained attention as antivirals when they demonstrated a high inhibitory effect in vitro against human immunodeficiency virus (HIV) and other enveloped viruses. However, that initial interest was followed by wide skepticism when in vivo assays refuted the initial results. In this paper we review the use of sulfated polysaccharides, and other polyanions, in antiviral therapy, focusing on extracellular polymeric substances (EPSs). We maintain that, in spite of those early difficulties, the use of polyanions and, specifically, the use of EPSs, in antiviral therapy should be reconsidered. We base our claim in several points. First, early studies showed that the main disadvantage of sulfated polysaccharides and polyanions is their low bioavailability, but this difficulty can be overcome by the use of adequate administration strategies, such as nebulization of aerosols to gain access to respiratory airways. Second, several sulfated polysaccharides and EPSs have demonstrated to be non-toxic in animals. Finally, these macromolecules are non-specific and therefore they might be used against different variants or even different viruses. [ABSTRACT FROM AUTHOR]

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus poses serious threats to the global public health and leads to worldwide crisis. No effective drug or vaccine is readily available. The viral RNA-dependent RNA polymerase (RdRp) is a promising therapeutic target. A hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected market available drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008μM and 9.453 μM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of fast and accurate anti-viral drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19. Author summary: Currently, a novel coronavirus called SARS-COV-2 is spreading across many parts of the world. Unfortunately, there is still a lack of effective drugs against the virus. Additionally, it usually takes much longer time to develop a new drug using traditional methods. Thus, it is now better to rely on some alternative methods to develop drugs that can treat such a disease effectively. In this paper, we have proposed a deep learning and molecular dynamics simulation based hybrid drug screening procedure for identifying potential drug candidates targeting RdRp from 1906 market available drugs. Our screening have successfully identified a FDA-approved drug called Pralatrexate that strongly inhibits the replication of 2019-nCoV in vitro with EC50 values of 0.008μM. This work demonstrated the feasibility of accurate virtual drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency. Here we report the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of Pibrentasvir, RNAs terminated with the active forms of the prodrugs Sofosbuvir, Remdesivir, Favipiravir, Molnupiravir and AT-527 were largely protected from excision by the exonuclease, while in the absence of Pibrentasvir, there was rapid excision. Due to its unique structure, Tenofovir-terminated RNA was highly resistant to exonuclease excision even in the absence of Pibrentasvir. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment. In this paper, the hepatitis C virus inhibitors Pibrentasvir and Ombitasvir are found to inhibit the SARS-CoV-2 exonuclease and are shown to have therapeutic potential when combined with SARS-CoV-2 polymerase inhibitors in viral cell cultures. [ABSTRACT FROM AUTHOR]

Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged = 18 years with initiation of symptoms = 9 days and SpO2 = 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial. [ABSTRACT FROM AUTHOR]

Background: The rising number of infections due to Severe Acute Respiratory Syndrome Coronavirus-2 (popularly known as COVID-19) has brought to the fore new antiviral drugs as possible treatments, including favipiravir. However, there is currently no data regarding the safety of this drug in patients with kidney impairment. The aim of this paper, therefore, is to share our experience of the use of favipiravir in pediatric patients affected by COVID-19 with any degree of kidney impairment. Methods: The study enrolled pediatric patients aged under 18 years and confirmed as suffering from COVID-19 and multisystem inflammatory syndrome in children (MIS-C) with any degree of kidney injury, who were treated with favipiravir at the time of admission. Results: Out of a total of 11 patients, 7 were diagnosed with MIS-C and 4 with severe COVID-19. The median age of the cases was 15.45 (9–17.8) years and the male/female ratio was 7/4. At the time of admission, the median serum creatinine level was 1.1 mg/dl. Nine patients were treated with favipiravir for 5 days, and 2 patients for 5 days followed by remdesivir for 5–10 days despite kidney injury at the time of admission. Seven patients underwent plasma exchange for MIS-C while 2 severely affected cases underwent continuous kidney replacement therapy (CKRT) as well. One severe COVID-19 patient received plasma exchange as well as CKRT. Serum creatinine values returned to normal in mean 3.07 days. Conclusions: Favipiravir seems a suitable therapeutic option in patients affected by COVID-19 with kidney injury without a need for dose adjustment. [ABSTRACT FROM AUTHOR]

The coronavirus pandemic has had a huge impact on public health with over 165 million people infected, 3.4 million deaths and a hugely deleterious effect on most economies. While vaccination effectively protects against the disease it is likely that viruses will evolve that can replicate in hosts immunised with the present vaccines. Thus, there is a great unmet need for effective antivirals that can block the development of serious disease in infected patients. The seven papers published in this issue of the Biochemical Journal address this need by expressing and purifying components required for viral replication, developing biochemical assays for these components and using the assays to screen a library of pre-existing pharmaceuticals for drugs that inhibited the target in vitro and inhibited viral replication in cell culture. The candidate drugs obtained are potential antivirals that may protect against SARS-CoV-2 infection. While not all the antiviral candidates will make it through to the clinic, they will be useful tool compounds and can act as the starting point for further drug discovery programmes. [ABSTRACT FROM AUTHOR]

Coronavirus Disease 2019 (COVID-19), first reported in December 2019 from Wuhan in China, had reached the stage of a pandemic. To date (28.06.2021), there are more than 181.9 million confirmed cases of the disease in the world. Even though vaccines have been developed, antiviral drugs are yet to be developed for management and treatment of SARS-CoV-2. Since several medicinal plants are used in traditional medicines, though with controversial efficacy claims, they can be considered as sources of new antiviral drug compounds against emerging viruses. In this context, spices are noteworthy as their anti-oxidant, anti-viral, anti-inflammatory and immunostimulatory properties are well studied and documented. The emerging scientific literature includes a number of papers on the anti-SARS-CoV-2 activity of spice extracts and specific compounds proven through different types of laboratory experiments. Here, the information pertaining to anti-viral properties of spice-based phytochemicals or natural compounds (not crude extracts) is summarized in this review. Spice-based compounds discussed here are an option for testing in COVID-19 patients though we don't have strong data to support their active recommendation. Because of their natural origin, safety, and low cost, they can be a viable option in our fight against viruses and this compilation may be useful for planning and designing more robust experiments in future. [ABSTRACT FROM AUTHOR]

Wuhan, a city of China, is the epicenter for the pandemic outbreak of coronavirus disease‐2019 (COVID‐19). It has become a severe public health challenge to the world and established a public health emergency of international worry. This infectious disease has pulled down the economy of almost all top developed nations. The coronaviruses (CoVs) known for various epidemics caused time to time. Infectious diseases such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), followed by COVID‐19, are all coronaviruses led outbreaks that scourged the history of mankind. CoVs evolved themselves to more infectious, transmissible, and more pandemic with time. To prevent the spread of the SARS‐CoV‐2, many countries have ordered the complete lockdown to combat the outbreak. This paper briefly discussed the historical background of CoVs and the evolution of human coronaviruses (HCoVs), the case studies and the development of their antiviral medications. The viral infection encountered with present‐day challenges and futuristic approaches with the help of nanotechnology to minimize the spread of infectious viruses. The antiviral drugs and their clinical advances, along with herbal medicines for viral inhibition and immunity boosters, are described. Elaboration of tables related to CoVs for the compilation of the literature has been adopted for the better understanding. [ABSTRACT FROM AUTHOR]

In December 2019, a novel coronavirus SARS-CoV-2, causing the disease COVID-19, spread from Wuhan throughout China and has infected people over 200 countries. Thus far, more than 3,400,000 cases and 240,000 deaths have occurred worldwide, and the coronavirus pandemic continues to grip the globe. While numbers of cases in China have been steadying, the number of infections outside China is increasing at a worrying pace. We face an urgent need to control the spread of the COVID-19 epidemic, which is currently expanding to a global pandemic. Efforts have focused on testing antiviral drugs and vaccines, but there is currently no treatment specifically approved. Traditional Chinese medicine (TCM) is grounded in empirical observations and the Chinese people use TCM to overcome these sorts of plagues many times in thousands of years of history. Currently, the Chinese National Health Commission recommended a TCM prescription of Qing-Fei-Pai-Du-Tang (QFPDT) in the latest version of the "Diagnosis and Treatment guidelines of COVID-19" which has been reported to provide reliable effects for COVID-19. While doubts about TCM still exist today, this review paper will describe the rationalities that QFPDT is likely to bring a safe and effective treatment of COVID-19. [ABSTRACT FROM AUTHOR]

For almost a year, humanity has been threatened by the new coronavirus known as SARS-CoV-2, which originated in China, and from there has spread to almost all regions around the globe. The incidence and mortality of this dangerous virus, which have recently increased in countries like Colombia, has overwhelmed public health systems and has created enormous difficulties and challenges at the economic, social, and political levels. With the aim of quickly finding treatment alternatives, running parallel to prevention initiatives spurred by the arrival of an effective vaccine, computational biology and computer-aided technologies have now been playing a booming role and have rapidly positioned themselves as key players in the pharmaceutical industry. This paper presents the main findings of a study focused on designing and discovering new agents with inhibitory capacity against the new coronavirus, describing the methodological strategy employed and presenting the implications, challenges, and future perspectives associated with finding a molecule with promising therapeutic potential. [ABSTRACT FROM AUTHOR]

Background: Actual level of knowledge of treatment of COVID-19 disease caused by a type of coronavirus is that the disease cannot at present be cured by targeted therapy. Worldwide research is aiming to find a specific treatment, such as a vaccine or drug, for this type of coronavirus; this may help improve the situation, but it is highly expensive and time-consuming. The purpose of this paper is to review drug therapies approved in different parts of the world to treat COVID-19 and draw attention to ototoxicity as one of the adverse side-effects. Material and methods: Review of current literature was done in the scientific databases PubMed, ResearchGate, GoogleScholar, and Science-Direct. Studies were reviewed with reference to the inclusion criteria, then graded to assess the internal and external validity, leaving 50 studies for review. Results: According to scientific reports, possible antiviral pharmacological agents to treat COVID-19 consist of chloroquine, hydroxychloroquine, azitromycine, oseltamivir, and tocilizumab. In some cases, certain combinations may lead to additive ototoxicity as an adverse effect. Ototoxicity may be manifested by sensory and nervous hearing loss, tinnitus, imbalance, and cochlear-mandibular symptoms, which are sometimes temporary but sometimes permanent. Conclusion: Drug ototoxicity is well known as a cause of cochlear hearing loss, and so the use of new pharmacotherapy methods and drug combinations in the fight against the new coronavirus may have harmful effects. Ototoxicity needs to be taken into account. [ABSTRACT FROM AUTHOR]

Nitazoxanide (NTZ), a promising antiviral agent, is currently being tested in clinical trials as a potential treatment for novel coronavirus disease 2019 (COVID -19). This paper describes a one-pot hydrothermal synthesis to prepare molybdenum (Mo)-doped manganese tungstate nanocubes (Mo–MnWO 4 NCs) for the electrochemical sensing of NTZ. The as-prepared Mo–MnWO 4 NCs were characterized using various techniques such as XRD, Raman, FE-SEM, FE-TEM, and XPS to confirm the crystal structure, morphology, and elemental composition. The obtained results demonstrate that Mo doping on MnWO 4 generates many vacancy sites, exhibiting remarkable electrochemical activity. The kinetic parameters of the electrode modified with Mo–MnWO 4 NCs were calculated to be (Ks) 1.1 × 10−2 cm2 s−1 and (α) 0.97, respectively. Moreover, a novel electrochemical sensor using Mo–MnWO 4 NCs was fabricated to detect NTZ, which is used as a primary antibiotic to control COVID-19. Under optimal conditions, the electrochemical reduction of NTZ was determined with a low detection limit of 3.7 nM for a linear range of 0.014–170.2 μM with a high sensitivity of 0.78 μA μM−1 cm−2 and negligible interference with other nitro group-containing drugs, cations, and anions. The electrochemical sensor was successfully used to detect NTZ in the blood serum and urine samples and achieved high recoveries in the range of 94–99.2% and 95.3–99.6%, respectively. This work opens a way to develop high-performance sensing materials by exploring the introduction of defect engineering on metal tungstates to detect drug molecules for practical applications. [Display omitted] • The Mo doped MnWO 4 NCs were prepared by simple and inexpensive hydrothermal synthesis method. • A new electrochemical sensor (Mo–MnWO 4 /GCE) was developed for detection of the COVID-19 drug nitazoxanide (NTZ). • The Mo–MnWO 4 /GCE exhibits good electrocatalytic activity towards NTZ detection in biological samples. • A promising sensing device for detection of drugs by exploring the defect engineering on metal tungstates. [ABSTRACT FROM AUTHOR]

COVID-19 has spread around the world and caused serious public health and social problems. Although several vaccines have been authorized for emergency use, new effective antiviral drugs are still needed. Some repurposed drugs including Chloroquine, Hydroxychloroquine and Remdesivir were immediately used to treat COVID-19 after the pandemic. However, the therapeutic effects of these drugs have not been fully demonstrated in clinical studies. In this paper, we found an antimalarial drug, Naphthoquine, showed good broad-spectrum anti-coronavirus activity. Naphthoquineinhibited HCoV-229E, HCoV-OC43 and SARS-CoV-2 replication in vitro, with IC50 = 2.05 ± 1.44 μM, 5.83 ± 0.74 μM, and 2.01 ± 0.38 µM, respectively. Time-of-addition assay was also performed to explore at which stage Naphthoquine functions during SARS-CoV-2 replication. The results suggested that Naphthoquine may influence virus entry and post-entry replication. Considering the safety of Naphthoquine was even better than that of Chloroquine, we think Naphthoquine has the potential to be used as a broad-spectrum drug for coronavirus infection. [ABSTRACT FROM AUTHOR]

The astonishing outbreak of SARS-CoV-2 coronavirus, known as COVID-19, has attracted numerous research interests, particularly regarding fabricating antimicrobial surface coatings. This initiative is aimed at overcoming and minimizing viral and bacterial transmission to the human. When contaminated droplets from an infected individual land onto common surfaces, SARS-CoV-2 coronavirus is able to survive on various surfaces for up to 9 days. Thus, the possibility of virus transmission increases after touching or being in contact with contaminated surfaces. Herein, we aim to provide overviews of various types of antiviral and antimicrobial coating agents, such as antimicrobial polymer-based coating, metal-based coating, functional nanomaterial, and nanocomposite-based coating. The action mode for each type of antimicrobial agent against pathogens is elaborated. In addition, surface properties of the designed antiviral and antimicrobial polymer coating with their influencing factors are discussed in this review. This paper also exhibits several techniques on surface modification to improve surface properties. Various developed research on the development of antiviral/antimicrobial polymer coating to curb the COVID-19 pandemic are also presented in this review. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance has emerged as a global health crisis and, therefore, new drug discovery is a paramount need. Cannabis sativa contains hundreds of chemical constituents produced by secondary metabolism, exerting outstanding antimicrobial, antiviral, and therapeutic properties. This paper comprehensively reviews the antimicrobial and antiviral (particularly against SARS-CoV-2) properties of C. sativa with the potential for new antibiotic drug and/or natural antimicrobial agents for industrial or agricultural use, and their therapeutic potential against the newly emerged coronavirus disease (COVID-19). Cannabis compounds have good potential as drug candidates for new antibiotics, even for some of the WHO's current priority list of resistant pathogens. Recent studies revealed that cannabinoids seem to have stable conformations with the binding pocket of the Mpro enzyme of SARS-CoV-2, which has a pivotal role in viral replication and transcription. They are found to be suppressive of viral entry and viral activation by downregulating the ACE2 receptor and TMPRSS2 enzymes in the host cellular system. The therapeutic potential of cannabinoids as anti-inflammatory compounds is hypothesized for the treatment of COVID-19. However, more systemic investigations are warranted to establish the best efficacy and their toxic effects, followed by preclinical trials on a large number of participants. [ABSTRACT FROM AUTHOR]

COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as 'molecule of hope' for the treatment of this disease. USFDA gave emergency approval to this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir. [ABSTRACT FROM AUTHOR]

A newly diagnosed coronavirus in 2019 (COVID-19) has affected all human activities since its discovery. Flavonoids commonly found in the human diet have attracted a lot of attention due to their remarkable biological activities. This paper provides a comprehensive review of the benefits of flavonoids in COVID-19 disease. Previously-reported effects of flavonoids on five RNA viruses with similar clinical manifestations and/or pharmacological treatments, including influenza, human immunodeficiency virus (HIV), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, were considered. Flavonoids act via direct antiviral properties, where they inhibit different stages of the virus infective cycle and indirect effects when they modulate host responses to viral infection and subsequent complications. Flavonoids have shown antiviral activity via inhibition of viral protease, RNA polymerase, and mRNA, virus replication, and infectivity. The compounds were also effective for the regulation of interferons, pro-inflammatory cytokines, and sub-cellular inflammatory pathways such as nuclear factor-κB and Jun N-terminal kinases. Baicalin, quercetin and its derivatives, hesperidin, and catechins are the most studied flavonoids in this regard. In conclusion, dietary flavonoids are promising treatment options against COVID-19 infection; however, future investigations are recommended to assess the antiviral properties of these compounds on this disease. [ABSTRACT FROM AUTHOR]

This paper reports the synthesis of branched alkylene guanidines using microfluidic technologies. We describe the preparation of guanidine derivatives at lower temperatures, and with significantly less time than that required in the previously applicable method. Furthermore, the use of microfluidics allows the attainment of high-purity products with a low residual monomer content, which can expand the range of applications of this class of compounds. For all the samples obtained, the molecular-weight characteristics are calculated, based on which the optimal condensation conditions are established. Additionally, in this work, the antiviral activity of the alkylene guanidine salt against the SARS-CoV-2 virus is confirmed. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

In this review, we present the environmental perspectives of the viruses and antiviral drugs related to SARS-CoV-2. The present review paper discusses occurrence, fate, transport, susceptibility, and inactivation mechanisms of viruses in the environment as well as environmental occurrence and fate of antiviral drugs, and prospects (prevalence and occurrence) of antiviral drug resistance (both antiviral drug resistant viruses and antiviral resistance in the human). During winter, the number of viral disease cases and environmental occurrence of antiviral drug surge due to various biotic and abiotic factors such as transmission pathways, human behaviour, susceptibility, and immunity as well as cold climatic conditions. Adsorption and persistence critically determine the fate and transport of viruses in the environment. Inactivation and disinfection of virus include UV, alcohol, and other chemical-base methods but the susceptibility of virus against these methods varies. Wastewater treatment plants (WWTPs) are major reserviors of antiviral drugs and their metabolites and transformation products. Ecotoxicity of antiviral drug residues against aquatic organisms have been reported, however more threatening is the development of antiviral resistance, both in humans and in wild animal reservoirs. In particular, emergence of antiviral drug-resistant viruses via exposure of wild animals to high loads of antiviral residues during the current pandemic needs further evaluation. ga1 • We analysed environmental perspectives of antiviral drugs and SARS-CoV-2. • Susceptibility and inactivation causes seasonality in the prevalence of SARS-CoV-2. • Surface-charge interactions govern environmental fate and transport of SARS-CoV-2. • Unprecedented use of antiviral drugs is hazardous to the environment. • Emergence of antiviral drug-resistant viruses needs further investigations. [ABSTRACT FROM AUTHOR]

We report here the synthesis, purification, and characterization of mono- and di-fatty acyl conjugates of remdesivir (RDV) and their in vitro antiviral activity against SAR-CoV-2, an Ebola virus transcription- and replication-competent virus-like particle (trVLP) system, and infectious Ebola virus. The most potent monofatty acyl conjugate was 4b, containing a 4-oxatetradecanolyl at the 3′ position. Monofatty acyl conjugates, 3′- O -tetradecanoyl (4a) (IC 50(VeroE6) = 2.3 μM; IC 50(Calu3) = 0.24 μM), 3′- O -4-oxatetradodecanoyl (4b) (IC 50(VeroE6) = 2.0 μM; IC 50(Calu3) = 0.18 μM), and 3′- O -(12-ethylthiododecanoyl) (4e) (IC 50(VeroE6) = 2.4 μM; IC 50(Calu3) = 0.25 μM) derivatives exhibited less activity than RDV (IC 50(VeroE6) = 0.85 μM; IC 50(Calu3) = 0.06 μM) in both VeroE6 and Calu3 cells. Difatty acylation led to a significant reduction in the antiviral activity of RDV (as shown in conjugates 5a and 5b) against SARS-CoV-2 when compared with monofatty acylation (3a-e and 4a-e). About 77.9% of 4c remained intact after 4 h incubation with human plasma while only 47% of parent RDV was observed at the 2 h time point. The results clearly indicate the effectiveness of fatty acylation to improve the half-life of RDV. The antiviral activities of a number of monofatty acyl conjugates of RDV, such as 3b , 3e , and 4b , were comparable with RDV against the Ebola trVLP system. Meanwhile, the corresponding physical mixtures of RDV and fatty acids 6a and 6b showed 1.6 to 2.2 times less antiviral activity than the corresponding conjugates, 4a and 4c , respectively, against SARS-CoV-2 in VeroE6 cells. A significant reduction in viral RNA synthesis was observed for selected compounds 3a and 4b consistent with the IC 50 results. These studies indicate the potential of these compounds as long-acting antiviral agents or prodrugs of RDV. [Display omitted] • Fatty acylation of free remdesivir (RDV) offered two structural conjugates. • 2D H–HCOSY, HSQC, and HMBC confirmed the structure of each isomer. • Conjugates of RDV with fatty acids were evaluated against SARS-CoV-2 and EBOV. • 3′-(4-Oxatetradecanolyl) of RDV was most effective against SARS-CoV-2. • Some fatty acyl conjugates of RDV showed comparable anti-EBOV activity with RDV. [ABSTRACT FROM AUTHOR]