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[Display omitted] • Viral infection occurs via the S1 region domain binding (RBD) with ACE2 enzymes. • Epidemiology suggest folic acid (FA) offers protection against Wuhan-SARS-CoV-2. • Simulations suggest that FA metabolite dihydrofolate (DHF) is the inhibiting agent. • Raman Spectroscopy Unveils DHF's Interference with SARS-CoV-2 Viral Attachment. • DHF Acts as a Barrier Against SARS-CoV-2 Attachment. Emerging evidence suggests that elevated levels of folic acid in the bloodstream may confer protection against Wuhan-SARS-CoV-2 infection and mitigate its associated symptoms. Notably, two comprehensive studies of COVID-19 patients in Israel and UK uncovered a remarkable trend, wherein individuals with heightened folic acid levels exhibited only mild symptoms and necessitated no ventilatory support. In parallel, research has underscored the potential connection between decreased folic acid levels and the severity of Covid-19 among hospitalized patients. Yet, the underlying mechanisms governing this intriguing inhibition remain elusive. In a quest to elucidate these mechanisms, we conducted a molecular dynamics simulation approach followed by a Raman spectroscopy study to delve into the intricate interplay between the folic acid metabolite, 7,8-dihydrofolate (DHF), and the angiotensin-converting enzyme ACE2 receptor, coupled with its interaction with the receptor-binding domain (RBD) of the Wuhan strain of SARS-CoV-2. Through a meticulous exploration, we scrutinized the transformation of the ACE2 + RBD complex, allowing these reactants to form bonds. This was juxtaposed with a similar investigation where ACE2 was initially permitted to react with DHF, followed by the exposure of the ACE2 + DHF complex to RBD. We find that DHF, when bonded to ACE2, functions as a physical barrier, effectively inhibiting the binding of the Wuhan strain RBD. This physicochemical process offers a cogent explanation for the observed inhibition of host cell infection in subjects receiving supplementary folic acid doses, as epidemiologically substantiated in multiple studies. This study not only sheds light on a potential avenue for mitigating SARS-CoV-2 infection but also underscores the crucial role of folic acid metabolites in host-virus interactions. This research paves the way for novel therapeutic strategies in the battle against COVID-19 and reinforces the significance of investigating the molecular mechanisms underlying the protective effects of folic acid in the context of viral infections. [ABSTRACT FROM AUTHOR]

The nCOVID-19 pandemic initiated its course of contagion from the city of Wuhan and now it has spread all over the globe. SARS-CoV-2 is the causative virus and the infection as well as its symptoms are distributed across the multi-organ perimeters. Interactions between the host and virus governs the induction of 'cytokine storm' resulting various immunopathological consequences leading to death. Till now it has caused tens of millions of casualties and yet no credible cure has emerged to vision. This article presents a comprehensive overview on the two most promising remedial approaches that are being attempted for the management, treatment, and plausible cure of nCOVID-19. In this context, chemotherapeutic approach primarily aims to interrupt the interactions between the host and the virus causing inhibition of its entry into the host cell and/or its proliferation and suppressing the inflammatory milieu in the infected patients. On the other side, immunotherapeutic approaches aim to modulate the host immunity by fine tuning the inflammatory signaling cascades to achieve phylaxis from the virus and restoring immune-homeostasis. Considering most of the path-breaking findings, combinatorial therapy involving of chemotherapeutics as well as vaccine could usher to be a hope for all of us to eradicate the crisis [ABSTRACT FROM AUTHOR]

Since 2003, we have seen the emergence of novel viruses, such as SARS-CoV-1, MERS, ZIKA, swine flu virus H1N1, Marburg, Monkeypox, Ebola, and SARS-CoV-2, but none of them gained pandemic proportions similar to SARS-CoV-2. This could be attributed to unique viral traits, allowing its rapid global dissemination following its emergence in October 2019 in Wuhan, China, which appears to be primarily driven by the emergence of highly transmissible and virulent variants that also associate, in some cases, with severe disease and considerable mortality caused by fatal pneumonia, acute respiratory distress syndrome (ARDS) in infected individuals. Mechanistically, several factors are involved in viral pathogenesis, and epigenetic alterations take the front seat in host-virus interactions. The molecular basis of all viral infections, including SARS-CoV-2, tightly hinges on the transitory silencing of the host gene machinery via epigenetic modulation. SARS-CoV-2 also hijacks and subdues the host gene machinery, leading to epigenetic modulation of the critical host elements responsible for antiviral immunity. Epigenomics is a powerful, unexplored avenue that can provide a profound understanding of virus-host interactions and lead to the development of epigenome-based therapies and vaccines to counter viruses. This review discusses current developments in SARS-CoV-2 variation and its role in epigenetic modulation in infected hosts. This review provides an overview, especially in the context of emerging viral strains, their recombinants, and their possible roles in the epigenetic exploitation of host defense and viral pathogenesis. It provides insights into host-virus interactions at the molecular, genomic, and immunological levels and sheds light on the future of epigenomics-based therapies for SARS-CoV-2 infection. • SARS-CoV-2 manipulates the host gene machinery through epigenetic alterations and modulatesl critical host elements responsible for antiviral immunity. • Unique viral traits, including recombination among variants, have driven the rapid global dissemination of SARS-CoV-2, and these traits could be associated with severe disease, and mortality. • Conceptually, the potential of epigenome-based therapies for treating SARS-CoV-2 infection is a likely possibility. [ABSTRACT FROM AUTHOR]

Nanodecoy systems based on analogues of viral cellular receptors assembled onto fluid lipid-based membranes of nano/extravescicles are potential new tools to complement classic therapeutic or preventive antiviral approaches. The need for lipid-based membranes for transmembrane receptor anchorage may pose technical challenges along industrial translation, calling for alternative geometries for receptor multimerization. Here we developed a semisynthetic self-assembling SARS-CoV-2 nanodecoy by multimerizing the biotin labelled virus cell receptor -ACE2- ectodomain onto a poly-avidin nanoparticle (NP) based on the Avidin-Nucleic-Acid-NanoASsembly-ANANAS. The ability of the assembly to prevent SARS-CoV-2 infection in human lung cells and the affinity of the ACE2:viral receptor-binding domain (RBD) interaction were measured at different ACE2:NP ratios. At ACE2:NP = 30, 90 % SARS-CoV-2 infection inhibition at ACE2 nanomolar concentration was registered on both Wuhan and Omicron variants, with ten-fold higher potency than the monomeric protein. Lower and higher ACE2 densities were less efficient suggesting that functional recognition between multi-ligand NPs and multi-receptor virus surfaces requires optimal geometrical relationships. In vivo studies in mice showed that the biodistribution and safety profiles of the nanodecoy are potentially suitable for preventing viral infection upon nasal instillation. Viral receptor multimerization using ANANAS is a convenient process which, in principle, could be rapidly adapted to counteract also other viral infections. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite the advances in contemporary medicine and availability of numerous innovative therapies, effective treatment and prevention of SARS-CoV-2 infections pose a challenge. In the search for new anti-SARS-CoV-2 drug candidates, natural products are frequently explored. Here, fifteen cyanopeptolins (CPs) were isolated from the Baltic cyanobacterium Nostoc edaphicum and tested against SARS-CoV-2. Of these depsipeptides, the Arg-containing structural variants showed the strongest inhibition of the Delta SARS-CoV-2 infection in A549ACE2/TMPRSS2 cells. The functional assays indicated a direct interaction of the Arg-containing CP978 with the virions. CP978 also induced a significant decline in virus replication in the primary human airway epithelial cells (HAE). Of the four tested SARS-CoV-2 variants, Wuhan, Alpha, Omicron and Delta, only Wuhan was not affected by CP978. Finally, the analyses with application of confocal microscopy and with the SARS-CoV-2 pseudoviruses showed that CP978-mediated inhibition of viral infection results from the direct binding of the cyanopeptolin with the coronaviral S protein. Considering the potency of viral inhibition and the mode of action of CP978, the significance of the peptide as antiviral drug candidate should be further explored. [ABSTRACT FROM AUTHOR]

In December 2019, an atypical pneumonia invaded the city of Wuhan, China, and the causative agent of this disease turned out to be a new coronavirus. In January 2020, the World Health Organization named the new coronavirus 2019-nCoV and subsequently it is referred to as SARS-CoV2 and the related disease as CoViD-19 (Lai et al., 2020). Very quickly, the epidemic led to a pandemic and it is now a worldwide emergency requiring the creation of new antiviral therapies and a related vaccine. The purpose of this article is to review and investigate further the molecular mechanism by which the SARS-CoV2 virus infection proceeds via the formation of a hetero-trimer between its protein S, the ACE2 receptor and the B0AT1 protein, which is the "entry receptor" for the infection process involving membrane fusion (Li et al., 2003). A reverse engineering process uses the formalism of the Hill function to represent the functions related to the dynamics of the biochemical interactions of the viral infection process. Then, using a logical evaluation of viral density that measures the rate at which the cells are hijacked by the virus (and they provide a place for the virus to replicate) and considering the "time delay" given by the interaction between cell and virus, the expected duration of the incubation period is predicted. The conclusion is that the density of the virus varies from the "exposure time" to the "interaction time" (virus-cells). This model can be used both to evaluate the infectious condition and to analyze the incubation period. The ongoing threat of the new coronavirus SARS-CoV2 pandemic is alarming and strategies for combating infection are highly desired. This RNA virus belongs to the β-coronavirus genus and is similar in some features to SARS-CoV. Currently, no vaccine or approved medical treatment is available. The complex dynamics of the rapid spread of this virus can be demonstrated with the aid of a computational framework. A mathematical model based on the principles of cell-virus interaction is developed in this manuscript. The amino acid sequence of S proein and its interaction with the ACE-2 protein is mimicked with the aid of Hill function. The mathematical model with delay is solved with the aid of numerical solvers and the parametric values are obtained with the help of MCMC algorithm. A delay differential equation model is developed to demonstrate the dynamics of target cells, infected cells and the SARS-CoV2. The important parameters and coefficients are demonstrated with the aid of numerical computations. The resulting thresholds and forecasting may prove to be useful tools for future experimental studies and control strategies. From the analysis, I is concluded that control strategy via delay is a promising technique and the role of Hill function formalism in control strategies can be better interpreted in an inexpensive manner with the aid of a theoretical framework. [ABSTRACT FROM AUTHOR]

The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. In the current review, we summarize and comparatively analyze the emergence and pathogenicity of COVID-19 infection and previous human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). We also discuss the approaches for developing effective vaccines and therapeutic combinations to cope with this viral outbreak. [ABSTRACT FROM AUTHOR]

The recent pandemic caused by SARS-CoV-2 has now spread worldwide and caused more than 51,000 deaths, by April 2nd 2020. As predicted, there are several obstacles for medical and governmental authorities to efficiently manage this respiratory illness. In spite of appropriated supplies, most hospitals are suffering from a scarcity of free beds, protective masks, sanitizing liquids and even ECMO machines for patients with severe cases. Defeating this pandemic is impossible without united and coordinated international attempts shaped by all countries of the world. We believe that an international scaled-determination is required to diminish the complex impacts of pandemic. The most important priorities are supposed to be i) The development of potential vaccine candidates to provide protection and interrupt the transmission of SARS-CoV-2, ii) To ensure enough supplies for hospitals and their homogeneous distribution among the countries with the worst number of severe cases, iii) There is a need for more studies to identify potential treatments that are effective for the control of this viral infection and iv) It is imperative to provide easy access to diagnostic kits for all countries affected by this pandemic. In the light of these suggestions, it would be recommendable to at least temporarily abandon the political checkouts in both national and international levels; therefore, all partners will be potentially able to efficiently enforce their strategies for the elimination of this unique threat to the human populations. [ABSTRACT FROM AUTHOR]

A significant number of SARS-CoV-2-infected individuals naturally overcome viral infection, suggesting the existence of a potent endogenous antiviral mechanism. As an innate defense mechanism, microRNA (miRNA) pathways in mammals have evolved to restrict viruses, besides regulating endogenous mRNAs. In this study, we systematically examined the complete repertoire of human miRNAs for potential binding sites on SARS-CoV-2 Wuhan-Hu-1, Beta, Delta, and Omicron. Human miRNA and viral genome interaction were analyzed using RNAhybrid 2.2 with stringent parameters to identify highly bonafide miRNA targets. Using publicly available data, we filtered for miRNAs expressed in lung epithelial cells/tissue and oral keratinocytes, concentrating on the miRNAs that target SARS-CoV-2 S protein mRNAs. Our results show a significant loss of human miRNA and SARS-CoV-2 interactions in Omicron (130 miRNAs) compared to Wuhan-Hu-1 (271 miRNAs), Beta (279 miRNAs), and Delta (275 miRNAs). In particular, hsa-miR-3150b-3p and hsa-miR-4784 show binding affinity for S protein of Wuhan strain but not Beta, Delta, and Omicron. Loss of miRNA binding sites on N protein was also observed for Omicron. Through Ingenuity Pathway Analysis (IPA), we examined the experimentally validated and highly predicted functional role of these miRNAs. We found that hsa-miR-3150b-3p and hsa-miR-4784 have several experimentally validated or highly predicted target genes in the Toll-like receptor, IL-17, Th1, Th2, interferon, and coronavirus pathogenesis pathways. Focusing on the coronavirus pathogenesis pathway, we found that hsa-miR-3150b-3p and hsa-miR-4784 are highly predicted to target MAPK13. Exploring miRNAs to manipulate viral genome/gene expression can provide a promising strategy with successful outcomes by targeting specific VOCs. • Hundreds of human miRs have putative binding sites on SARS-CoV-2 VOC genomes. • VOCs, particularly Omicron, evade miR binding sites identified in Wuhan-Hu-1. • SARS-CoV-2 targeting miRs regulate immune pathways, suggesting antiviral functions. [ABSTRACT FROM AUTHOR]

• The main protease (Mpro), from the SARS-CoV-2 replication cycle is found as close homolog to the Hepatitis C Virus (HCV) protease and could be susceptible to blocking its activity by DAAs. • In the current study, the DAAs were investigated as antivirals using structure based computational approach against Mpro of SARS-CoV-2 to propose them as new therapeutics. • Overall, the current study provides insight to combat COVID-19 using FDA-approved DAAs as repurposed drugs. A new coronavirus strain called as SARS-CoV-2 has emerged from Wuhan, China in late 2019 and it caused a worldwide pandemic in a few months. After the Second World War, it is the biggest calamity observed as there is no specific US Food and Drugs Administration (USFDA) approved drug or vaccine available globally for the treatment. Several clinical trials are ongoing for therapeutic alternatives, however with little success rate. Considering that the time is crucial, the drug repurposing and data obtained from in silico models are one of the most important approaches to identify possible lead inhibitors against SARS-CoV-2. More recently, the Direct Acting Antivirals (DAAs) are emerged as the most promising drugs to control viral infection. The Main Protease (Mpro), a key enzyme in the SARS-CoV-2 replication cycle, is found close homolog to the Hepatitis C Virus (HCV) protease and could be susceptible of blocking its activity by DAAs. In the current study, the DAAs were investigated as antivirals using structure based computational approach against Mpro of SARS-CoV-2 to propose them as new therapeutics. In total, 20 DAAs of HCV, including a reference compound O6K were docked against Mpro. The docked structures were examined and resulted in the identification of six highly promising DAAs i.e. beclabuvir, elbasvir, paritaprevir, grazoprevir, simeprevir, and asunapevir exhibiting high theoretical binding affinity to Mpro from SARS-CoV-2 in comparison to other DAAs. Furthermore, the post docking analysis revealed that Cys145, Glu166, His163, Thr26, His41, and Met165 played potential role for the binding of these DAAs inside binding site of Mpro. Furthermore, the correlation between binding energies were found in accord with the results from the reported IC 50 s for some DAAs. Overall, the current study provides insight to combat COVID-19 using FDA-approved DAAs as repurposed drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, in December 2019, and its global dissemination became the coronavirus disease 2019 (COVID-19) pandemic declared by the World Health Organization (WHO) on 11 March 2020. In patients undergoing immunotherapy, the effect and path of viral infection remain uncertain. In addition, viral-infected mice and humans show T-cell exhaustion, which is identified after infection with SARS-CoV-2. Notably, they regain their T-cell competence and effectively prevent viral infection when treated with anti-PD-1 antibodies. Four clinical trials are officially open to evaluate anti-PD-1 antibody administration's effectiveness for cancer and non-cancer individuals influenced by COVID-19 based on these findings. The findings may demonstrate the hypothesis that a winning strategy to combat SARS-CoV-2 infection could be the restoration of exhausted T-cells. In this review, we outline the potential protective function of the anti-PD-1 blockade against SARS-CoV-2 infection with the aim to develop SARS-CoV-2 therapy. [Display omitted] • The effect and course of viral infection in patients receiving immunotherapy are still unknown. • Anti-PD-1 antibody treatment is currently being evaluated in four clinical trials for cancer and non-cancer patients that have been affected by COVID-19. • We outline the potential protective role of the anti-PD-1 blockade against SARS-CoV-2 infection with the aim to develop SARS-CoV-2 treatment. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2020 and coronavirus disease 19 (COVID-19) was later announced as pandemic by the World Health Organization (WHO). Since then, several studies have been conducted on the prevention and treatment of COVID-19 by potential vaccines and drugs. Although, the governments and global population have been attracted by some vaccine production projects, the presence of SARS-CoV-2-specific antiviral drugs would be an urge necessity in parallel with the efficient preventive vaccines. Various nonspecific drugs produced previously against other bacterial, viral, and parasite infections were recently evaluated for treating patients with COVID-19. In addition to therapeutic properties of these anti-COVID-19 compounds, some adverse effects were observed in different human organs as well. Not only several attentions were paid to antiviral therapy and treatment of COVID-19, but also nanomedicine, immunotherapy, and cell therapy were conducted against this viral infection. In this review study, we planned to introduce the present and potential future treatment strategies against COVID-19 and define the advantages and disadvantages of each treatment strategy. [Display omitted] • Several studies have been conducted on the prevention and treatment of COVID-19 by potential vaccines and drugs. • There would be urgent planes to combat COVID-19 infection in parallel with prevention strategies such as vaccination. • Macrophage therapy, Immunotherapy of COVID-19 (plasma therapy, cytokine-based immunotherapy, cell therapy DC therapy, and NK cell therapy), and nano-based therapy are believed to be useful as other effective therapies during COV-19 pandemic. [ABSTRACT FROM AUTHOR]

Nine COVID-19 (Corona Virus Disease, 2019) cases were observed in one community in Guangzhou. All the cases lived in three vertically aligned units of one building sharing the same piping system, which provided one unique opportunity to examine the transmission mode of SARS-CoV-2. We interviewed the cases on the history of travelling and close contact with the index patients. Respiratory samples from all the cases were collected for viral phylogenetic analyses. A simulation experiment in the building and a parallel control experiment in a similar building were then conducted to investigate the possibility of transmission through air. Index patients living in Apartment 15-b had a travelling history in Wuhan, and four cases who lived in Apartment 25-b and 27-b were subsequently diagnosed. Phylogenetic analyses showed that virus of all the patients were from the same strain of the virus. No close contacts between the index cases and other families indicated that the transmission might not occur through droplet and close contacts. Airflow detection and simulation experiment revealed that flushing the toilets could increase the speed of airflow in the pipes and transmitted the airflow from Apartment 15-b to 25-b and 27-b. Reduced exhaust flow rates in the infected building might have contributed to the outbreak. The outbreak of COVID-19 in this community could be largely explained by the transmission through air, and future efforts to prevent the infection should take the possibility of transmission through air into consideration. A disconnected drain pipe and exhaust pipe for toilet should be considered in the architectural design to help prevent possible virus spreading through the air. • Provide evidence of SARS-CoV-2 transmission through air. • Poor ventilation in the apartments increases the risk of transmission. • Floor drain should be sealed with water and regular disinfected. • The privately remodeled piping system might have played a role in this transmission. [ABSTRACT FROM AUTHOR]

• The SARS-CoV-2 and dengue syndemic is a reality in several countries worldwide. • Prior dengue infection did not impact clinical parameters of COVID-19 patients. • Active dengue fever worsened the pulmonary function of COVID-19 patients. • Active and prior dengue infection were associated with an increase in blood glucose levels. Originated in Wuhan, China, the coronavirus 19 disease (COVID-19) has quickly spread worldwide, reaching countries that already faced other endemics and epidemics. In Brazil, such a concerning situation includes arboviruses, among which the dengue virus stands out. Here, we determined the rate of SARS-CoV-2/dengue virus co-infection in a total of 178 patients with COVID-19 symtoms admitted into a large public hospital of the Federal District of Brazil. Furthermore, we evaluated whether prior or active dengue virus infection influenced hematological, biochemical, and clinical parameters of such patients. One hundred and twelve (63%) individuals tested positive for COVID-19, of which 43 (38.4%) were co-infected with dengue virus, and 50 (44.6%) had antibodies indicative of previous dengue infection. Co-infected patients showed lower numbers of circulating lymphocytes and monocytes, higher glucose rates, and a worse pulmonary condition. Of note, prior infections with dengue virus did not influence clinical parameters, but active dengue fever resulted in higher hospitalization rate. In conclusion, amid the current complex epidemiological scenario in Brazil, our data support the notion that SARS-CoV-2 and dengue co-infection affects an important percentage of COVID-19 patients and leads to worse clinical parameters, requiring greater attention from health authorities. Image, graphical abstract [ABSTRACT FROM AUTHOR]

In the Fall of 2019 a sudden and dramatic outbreak of a pulmonary disease (Coronavirus Disease COVID-19), due to a new Coronavirus strain (i.e. , SARS-CoV-2), emerged in the continental Chinese area of Wuhan and quickly diffused throughout the world, causing up to now several hundreds of thousand deaths. As for common viral infections, the crucial event for the viral life cycle is the entry of genetic material inside the host cell, realized by the spike protein of the virus through its binding to host receptors and its activation by host proteases; this is followed by translation of the viral RNA into a polyprotein, exploiting the host cell machinery. The production of individual mature viral proteins is pivotal for replication and release of new virions. Several proteolytic enzymes either of the host and of the virus act in a concerted fashion to regulate and coordinate specific steps of the viral replication and assembly, such as (i) the entry of the virus, (ii) the maturation of the polyprotein and (iii) the assembly of the secreted virions for further diffusion. Therefore, proteases involved in these three steps are important targets, envisaging that molecules which interfere with their activity are promising therapeutic compounds. In this review, we will survey what is known up to now on the role of specific proteolytic enzymes in these three steps and of most promising compounds designed to impair this vicious cycle. [ABSTRACT FROM AUTHOR]

In the present situation, COVID-19 has become the global health concern due to its high contagious nature. It initially appeared in December 2019 in Wuhan, China and now affected more than 190 countries. As of now preventive measures are the sole solution to stop this disease for further transmission from person to person transmissions as there is no effective treatment or vaccine available to date. Research and development of new molecule is a laborious process; therefore, drug repurposing can be an alternative solution that involves the identification of potential compounds from the already available data. Alkaloids are potential source of therapeutic agents which might be able to treat novel COVID-19. Therefore, in the present study, twenty potential alkaloid molecules that possess antiviral activity against different viral diseases have taken into consideration and scrutinized using Lipinski's rule. Then out of twenty compounds seventeen were further selected for docking study. Docking study was performed using Autodock software and the best four molecule which provides maximum negative binding energy was selected for further analysis. Two alkaloids namely thalimonine and sophaline D showed potential activity to inhibit the Mpro but to confirm the claim further in-vitro studies are required. [ABSTRACT FROM AUTHOR]

The widespread problem of a 2019-novel coronavirus (SARS-CoV-2) strain outbreak in Wuhan, China has prompted a search for new drugs to protect against and treat this disease. It is necessary to immediately investigate this due to the mutation of the viral genome and there being no current protective vaccines or therapeutic drugs. Molecular modelling and molecular docking based on in silico screening strategies were employed to determine the potential activities of seven HIV protease (HIV-PR) inhibitors, two flu drugs, and eight natural compounds. The computational approach was carried out to discover the structural modes with a high binding affinity for these drugs on the homology structure of the Wuhan coronavirus protease (SARS-CoV-2 PR). From the theoretical calculations, all the drugs and natural compounds demonstrated various favorable binding affinities. An interesting finding was that the natural compounds tested had a higher potential binding activity with the pocket sites of SARS-CoV-2 PR compared to the groups of HIV-PR inhibitors. The binding modes of each complex illustrated between the drugs and compounds interacted with the functional group of amino acids in the binding pocket via hydrophilic, hydrophobic, and hydrogen bond interactions using the molecular dynamics simulation technique. This result supports the idea that existing protease inhibitors and natural compounds could be used to treat the new coronavirus. This report sought to provide fundamental knowledge as preliminary experimental data to propose an existing nutraceutical material against viral infection. Collectively, it is suggested that molecular modelling and molecular docking are suitable tools to search and screen for new drugs and natural compounds that can be used as future treatments for viral diseases. Image 1 • We generated several docked complexes in order to evaluate the potential activities of novel coronavirus protease (SARS-CoV-2 PR) inhibitors. • The calculations of the binding affinity were interestingly found to predict the drug activities using the theoretical calculations. • The binding mode of each complex was found to observe at the potential site with slightly different amino acid binding poses in the SARS-CoV-2 PR. • Here, we are able to propose the first structure-activity relationships of alternative usage of the natural materials. [ABSTRACT FROM AUTHOR]

In December 2019, a novel virus, namely COVID-19 caused by SARS-CoV-2, developed from Wuhan, (Hubei territory of China) used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Data revealed that the newly emerged SARS-CoV-2 affected more than 24,854,140 people with 838,924 deaths worldwide. Until now, no licensed immunization or drugs are present for the medication of SARS-CoV-2. The present review aims to investigate the latest developments and discuss the candidate antibodies in different vaccine categories to develop a reliable and efficient vaccine against SARS-CoV-2 in a short time duration. Besides, the review focus on the present challenges and future directions, structure, and mechanism of SARS-CoV-2 for a better understanding. Based on data, we revealed that most of the vaccines are focus on targeting the spike protein (S) of COVID-19 to neutralized viral infection and develop long-lasting immunity. Up to phase-1 clinical trials, some vaccines showed the specific antigen-receptor T-cell response, elicit the humoral and immune response, displayed tight binding with human-leukocytes-antigen (HLA), and recognized specific antibodies to provoke long-lasting immunity against SARS-CoV-2. Unlabelled Image • The latest developments and antibodies recommendations for a vaccine formulation against SARS-CoV-2 are studied. • The SARS-CoV-2 shared the more than 80% nucleotide sequence with SARS-CoV-1 and 90% to bat genome. • Over 115 companies started the work on different vaccine candidates to develop a strong vaccine. • Phase-1 clinical trials showed better results in provoking specific humoral and immune responses against SAR-CoV-2. • The ideal vaccine should be simple, easy to administrate, long-lasting, and well-coordinated with targets. [ABSTRACT FROM AUTHOR]

The emergence of a new coronavirus, in around late December 2019 which had first been reported in Wuhan, China has now developed into a massive threat to global public health. The World Health Organization (WHO) has named the disease caused by the virus as COVID-19 and the virus which is the culprit was renamed from the initial novel respiratory 2019 coronavirus to SARS-CoV-2. The person-to-person transmission of this virus is ongoing despite drastic public health mitigation measures such as social distancing and movement restrictions implemented in most countries. Understanding the source of such an infectious pathogen is crucial to develop a means of avoiding transmission and further to develop therapeutic drugs and vaccines. To identify the etiological source of a novel human pathogen is a dynamic process that needs comprehensive and extensive scientific validations, such as observed in the Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), and human immunodeficiency virus (HIV) cases. In this context, this review is devoted to understanding the taxonomic characteristics of SARS-CoV-2 and HIV. Herein, we discuss the emergence and molecular mechanisms of both viral infections. Nevertheless, no vaccine or therapeutic drug is yet to be approved for the treatment of SARS-CoV-2, although it is highly likely that new effective medications that target the virus specifically will take years to establish. Therefore, this review reflects the latest repurpose of existing antiviral therapeutic drug choices available to combat SARS-CoV-2. • Identify the dynamic etiological source of SARS-CoV-2 that needs comprehensive and extensive scientific validations. • HIV infected individuals need to be considered as a vulnerable group for SARS-CoV-2. • Crosstalk of molecular mechanisms and cell death of SARS-CoV-2 and HIV. • Clinical trials conducted on the repurposing of existing antiviral drugs, more insights into the pathobiology are required. [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 accompanied by >20 common seasonal acute viral respiratory infections in March-June 2020 in a Russian population. • 56.68% and 70.67% of SARS-CoV-2-positive individuals were asymptomatic in March and June 2020, respectively. • The population is gradually adapting to the novel pathogen, even in the absence of a vaccine. • 92.6% of COVID-19-related fatalities were associated with at least one clinically identified comorbidity. • Human respiratory syncytial virus and rhinoviruses accounted for the largest proportion of viral co-infections with SARS-CoV-2. This study was conducted to assess the spread of SARS-CoV-2 in Russia and the adaptation of the population to the virus in March to June 2020. Two groups were investigated: 1) 12 082 individuals already proven positive for SARS-CoV-2 (clinical information was studied); 2) 7864+4458 individuals with suspected respiratory infections (polymerase chain reaction [PCR] tests and clinical information were studied). In the latter, SARS-CoV-2-positive individuals comprised 5.37% in March and 11.42% in June 2020. Several viral co-infections were observed for SARS-CoV-2. Rhinoviruses accounted for the largest proportion of co-infections (7.91% of samples were SARS-CoV-2-positive); followed by respiratory syncytial virus (7.03%); adenoviruses (4.84%); metapneumoviruses (3.29%); parainfluenza viruses (2.42%); enterovirus D68 (1.10%) and other viruses (entero-, echo-, parecho-) (<1%). Average SARS-CoV-2 case fatality rate in the group of 12 537 individuals was determined to be 0.6% (in contrast to official Russian government statistics of 1.5% mortality). This rate is within the range of mortality caused by other common seasonal respiratory viruses (0.01-2.21% in Russia in 2012 to 2020). Most fatalities occurred in individuals with comorbidities, as for other respiratory viruses. The proportion of SARS-CoV-2 asymptomatic carriers was 56.68% in March and 70.67% in June 2020. This new pathogen presents a substantial risk to human beings as it was not contained at the start of its outbreak in Wuhan and spread worldwide. However, surveillance, prevention and treatment must be strictly evidence-based and not dictated by fear. [ABSTRACT FROM AUTHOR]

• COVID-19 is associated with cytokine storm, and eventually related to septic shock and ARDS. • Steroids are discouraged for use in viral lung infections, including COVID-19, with exceptions. • Corticosteroids are indicated for adults with refractory septic shock and moderate and severe ARDS. • Steroids are indicated for management of asthma and chronic obstructive pulmonary disease exacerbation. • Steroids reduced mortality in COVID-19 patients in need of supportive oxygenotherapy or invasive mechanical ventilation. In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Later described as COVID-19 (coronavirus disease 2019), this infection caused by a virus from the Coronaviridae family (SARS-CoV-2) has spread globally. Effective therapies for this new disease are urgently needed. In this short communication, we will evaluate the use of corticosteroids as an adjunctive pharmacological therapy in the management of COVID-19 and describe its pros and cons in light of the latest available evidence. [ABSTRACT FROM AUTHOR]

• Chloroquine (CQ) has diverse modes of action against viral infections. • CQ may interfere with SARS-CoV-2 attachment to the host ACE2 receptor. • CQ may hamper the STING pathway to attenuate the pro-inflammatory response. • Hydroxychloroquine (HCQ) might be a logical approach in the treatment of SARS-CoV-2 infection. • Large clinical trials are needed before clinical recommendations of HCQ against COVID-19. Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have long been used worldwide as frontline drugs for the treatment and prophylaxis of human malaria. Since the first reported cases in Wuhan, China, in late December 2019, humans have been under threat from coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 (previously known as 2019-nCoV), subsequently declared a pandemic. While the world is searching for expedited approval for a vaccine, which may be only preventative and not a cure, physicians and country leaders are considering several concerted clinical trials suggesting that the age-old antimalarial drugs CQ/HCQ could be a potent therapeutic against COVID-19. Based on accumulating scientific reports, here we highlight the possible modes of action of CQ/HCQ that could justify its use against viral infections. Considering the global health crisis of the COVID-19 pandemic, the option of repurposing old drugs, e.g. CQ/HCQ, particularly HCQ, for the treatment of SARS-CoV-2 infection could be a good choice. CQ/HCQ has diverse modes of action, including alteration of the acidic environment inside lysosomes and late endosomes, preventing endocytosis, exosome release and phagolysosomal fusion, and inhibition of the host cytokine storm. One or more diverse mechanisms might work against viral infections and reduce mortality. As there is no cure for COVID-19, clinical testing of HCQ is urgently required to determine its potency against SARS-CoV-2, as this is the currently available treatment option. There remains a need to find other innovative drug candidates as possible candidates to enter clinical evaluation and testing. [ABSTRACT FROM AUTHOR]

• The characteristics of 200 patients with COVID-19 in Yichang were analyzed. • COVID-19 was of clustering onset, and can cause severe respiratory disease and death. • The mortality of ICU patients confirmed with COVID-19 was considerably high. • The lymphocytes might be the main target of SARS-CoV-2 and this may be related to the severity and mortality of the disease. • The cytokine storm may be associated with the worsening of the disease. The recent outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide, with especially severe epidemics occurring in cities across China. To report the epidemiological and clinical futures of the 200 patients infected with COVID-19 in Yichang, Hubei Province, China. 200 patients confirmed with COVID-19 in a designated hospital in Yichang from Jan 30 to Feb 8, 2020 were investigated retrospectively. The epidemiological data and clinical characteristics were collected. The data between the ICU patients and non-ICU patients were compared. The patients were followed up till Feb 26, 2020. Of the 200 hospitalized patients with COVID-19, 98 (49.0 %) were male, and the mean age was 55 years. Eighty-seven (43.5 %) had no linkage to Wuhan or contact history. Familial clustering was found in 34 patients. Sixtyfive (32.5 %) suffered from chronic diseases. The common symptoms included fever (171[85.5 %]), cough (116[58.0 %]), and fatigue (64[32 %]). Most patients had lymphopenia. One hundred and seventy-two (86 %) patients showed typical imaging findings of viral pneumonia. Most patients received antiviral, antibiotic, and corticosteroid treatment. Compared with the non-ICU patients, 29 (14.5 %) patients in the ICU were older and more likely to show dyspnea and complications including ARDS. As of Feb 26, 15 (51.7 %) patients in the ICU had died. The COVID-19 infection was of clustering onset and can cause severe respiratory disease and even death. The mortality of ICU patients with COVID-19 was considerably high. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2, better known as COVID-19 has become the current health concern to the entire world. Initially appeared in Wuhan, China around December 2019, it had spread to almost 187 countries due to its high contagious nature. Precautionary measures remain the sole obliging tactic to cease the person to person transmissions till any effective method of treatment or vaccine is developed. Amidst the pandemic, research and development of new molecule is labour-intensive and tedious process. Drug repurposing is the concept of identifying therapeutically potent molecule from the library of pre-existing molecules. In the present study, 61 molecules that are already being used in clinics or under clinical scrutiny as antiviral agents are surveyed via docking study. Docking study was performed using Maestro interface (Schrödinger Suite, LLC, NY). Out of these 61 molecules, 37 molecules were found to interact with >2 protein structures of COVID-19. The docking results indicate that amongst the reported molecules, HIV protease inhibitors and RNA-dependent RNA polymerase inhibitors showed promising features of binding to COVID-19 enzyme. Along with these, Methisazone an inhibitor of protein synthesis, CGP42112A an angiotensin AT2 receptor agonist and ABT450 an inhibitor of the non-structural protein 3-4A might become convenient treatment option as well against COVID-19. The drug repurposing approach provide an insight about the therapeutics that might be helpful in treating corona virus disease. Unlabelled Image • Drug repurposing has become an emerging tactic to fight COVID-19. • Known antiviral agents used to study docking interaction with COVID-19 enzymes. • HIV protease inhibitors showed close interaction with COVID-19. • Methisazone, CGP42112A and ABT450 may become useful treatment against COVID-19. [ABSTRACT FROM AUTHOR]

• We first described the epidemiological characteristics of patients with SARS-CoV-2 in Hunan and these patients were early mild cases. • The clinical symptoms, laboratory results, and imaging reports of patients with COVID-19 in the Hunan area were different from Wuhan area. • For non-Wuhan epidemic areas, more attention should be paid to the nucleic acid test results of throat swabs and stools. • Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. • Attention should be paid to asymptomatic carriers, and this is of great significance for the control of the global epidemic. In December 2019, coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other regions. To describe the clinical manifestations and epidemiological characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Hunan Province in 2020. From January 19 to February 7, 2020, 33 patients with positive in nucleic acid test of pharyngeal swab were retrospectively collected and analyzed. There are 33 COVID-19 patients (16 male, 17 female), and the median age was 46 years. Nineteen patients (48 %) were associated with a family cluster outbreak. Seventeen patients (52 %) had traveled or lived in Hubei Province. These patients are early mild cases, most common symptoms are fever [23 (70 %)] and cough [13 (39 %)]. Most patients' white blood cell counts are normal, while they manifest as significant reduction in lymphocytes [17/28 (61 %)]. The levels of c-reactive protein and erythrocyte sedimentation rate suggest a typical viral infection. Procalcitonin did not increase and D-dimer increased slightly. Lactate dehydrogenase (LDH) levels have elevated in most patients. CT images of these patients showed bilateral multiple plaques or nodular ground-glass opacities (68.4 %). Fecal nucleic acid results were positive in eight COVID-19 patients accompanied with diarrhea. Tear nucleic acid results were negative in six COVID-19 patients. And four asymptomatic patients were infected with SARS-CoV-2. The clinical symptoms, laboratory results and imaging reports of patients with COVID-19 in Hunan area are significantly different from those in Wuhan area. For non-Wuhan epidemic areas, more attention should be paid to nucleic acid test results of throat swabs and stools, and it is not easily to diagnose based on clinical symptoms and CT results. Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. Attention should be paid to asymptomatic carriers, which is of great significance for the control of the global epidemic. [ABSTRACT FROM AUTHOR]

• Fever and cough are the most common symptoms in patients with COVID-19. • The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19. • ARDS and ACI may be the main obstacles to treatment recovery for patients. • The case severe rate and mortality is lower than that of SARS and MERS. Since being first reported in Wuhan, China, in December 8, 2019, the outbreak of the novel coronavirus, now known as COVID-19, has spread globally. Some case studies regarding the characteristics and outcome of patients with COVID-19 have been published recently. We conducted a meta-analysis to evaluate the risk factors of COVID-19. Medline, SinoMed, EMBASE, and Cochrane Library were searched for clinical and epidemiological studies on confirmed cases of COVID-19. The incidence of fever, cough, fatigue, and dyspnea symptoms were 85.6 % (95CI 81.3–89.9 %), 65.7 % (95CI 60.1–71.4 %), 42.4 % (95CI 32.2–52.6 %) and 21.4 % (95CI 15.3–27.5 %). The prevalence of diabetes was 7.7 % (95CI 6.1–9.3 %), hypertension was 15.6 % (95CI 12.6–18.6 %), cardiovascular disease was 4.7 % (95CI 3.1–6.2 %), and malignancy was 1.2 % (95CI 0.5–1.8 %). The complications, including ARDS risk, ranged from 5.6–13.2 %, with the pooled estimate of ARDS risk at 9.4 %, ACI at 5.8 % (95CI 0.7–10.8 %), AKI at 2.1 % (95CI 0.6–3.7 %), and shock at 4.7 % (95CI 0.9–8.6 %). The risks of severity and mortality ranged from 12.6 to 23.5% and from 2.0 to 4.4 %, with pooled estimates at 18.0 and 3.2 %, respectively. The percentage of critical cases in diabetes and hypertension was 44.5 % (95CI 27.0–61.9 %) and 41.7 % (95CI 26.4–56.9 %), respectively. Fever is the most common symptom in patients with COVID-19. The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19. ARDS and ACI may be the main obstacles for patients to treatment recovery. The case severe rate and mortality is lower than that of SARS and MERS. [ABSTRACT FROM AUTHOR]

• This study is currently the largest case series to date on the RT-PCR findings of COVID-19 throughout disease course. • The average contagious period of infected patients was 20 days. • Longer observation period and more than 2 series of negative viral test are necessary for patients ≥65 years. With the spread of Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, its effect on society is amplified. We aimed to describe the viral detection results across different timepoints throughout the disease course. A retrospective study of 301 confirmed COVID-19 patients hospitalized at Tongji Hospital in Wuhan, China, were included. Demographic characteristics of the patients were collected. Upper respiratory specimens (throat and/or nasal swabs) were obtained and analyzed by real-time RT-PCR for SARS-CoV-2 infection. Period of viral infection and the contagious stage were analyzed. Of 301 hospitalized COVID-19 patients, the median age was 58 years and 51.2 % were male. The median period between symptoms presence and positive SARS-CoV-2 RT-PCR results was 16 days (IQR, 10–23, N = 301). The median period between symptoms presence and an effective negative SARS-CoV-2 RT-PCR result was 20 days (IQR, 17–24; N = 216). Infected patient ≥65 years old stayed contagious longer (22 days vs 19 days, p = 0.015). Although two consecutive negative results were confirmed in 70 patients, 30 % of them had positive viral test results for the third time. Using specimens from nasal swabs to run the RT-PCR test showed a higher positive rate than using specimens from throat swabs. This large-scale investigation with 1113 RT-PCR test results from 301 COVID-19 patients showed that the average contagious period of SARS-CoV-2 infected patients was 20 days. Longer observation period and more than 2 series of negative viral test are necessary for patients ≥65 years. [ABSTRACT FROM AUTHOR]

Alarms periodically emerge for viral pneumonia infections due to coronavirus. In all cases, these are zoonoses passing the barrier between species and infect humans. The legitimate concern of the international community is due to the fact that the new identified coronavirus, named SARS-CoV-2 (previously called 2019-nCoV), has a quite high mortality rate, around 2%, and a strong ability to spread, with an estimated reproduction number higher than 2. Even though all countries are doing their utmost to stop the pandemic, the only reliable solution to tackle the infection is the rapid development of a vaccine. For this purpose, the means of bioinformatics, applied in the context of reverse-vaccinology paradigm, can be of fundamental help to select the most promising peptides able to trigger an effective immune response. In this short report, using the concept of nullomer and introducing a distance from human self, we provide a list of peptides that could deserve experimental investigation in the view of a potential vaccine for SARS-CoV-2. [ABSTRACT FROM AUTHOR]

• Several studies suggested Baricitinib as a potential drug for the management of COVID 19 infection through drug repurposing strategies because of its ability to act on AT2 cells and AAK1 mediated endocytosis. • Baricitinib, a Januase Kinase Inhibitor, have known to cause Lymphocytopenia, Neutropenia and Viral Reactivation. • Reported Epidemiological studies have shown that COVID 19 patients have a lesser absolute lymphocyte count closer to the threshold value. • Moreover, incidence of Co-infection for COVID 19 patients is one of the leading causes of Mortality. Baricitinib may enhance the incidence of Co-infection. • Hence, Baricitinib may not be an ideal option for Management of COVID 19. The Wuhan outbreak of novel Corona virus infection has been the global focus since December 2019. This infection has become a global pandemic. It is highly important to understand the virology of the pathogen and to explore the therapeutic options for management of this pandemic. Drug repurposing strategies are being considered for management of COVID 19. Among the identified drugs, Baricitinib has become a keen interest for researchers because of its ability to inhibit the viral assembly by the prevention of Clarithrin associated endocytosis. We tried to explore the reasons on why Baricitinib is not an ideal option for COVID 19. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) is highly pathogenic viral infection caused by SARS-CoV-2. Currently, COVID-19 has caused global health concern. It is assumed that COVID-19 has zoonotic origin based on the large number of infected people who were exposed to the wet market in Wuhan City, China. The phylogenetic analysis has revealed that SARS-CoV-2 has significant sequence similarity with severe acute respiratory syndrome-like (SARS-like) bat viruses, thus bats could be primary possible reservoir. The intermediate host and there subsequent transfer is not known yet, although human to human transfer is widely confirmed. The transmission of COVID-19 infection from one person to another resulted in the isolation of patients who were subsequently given a variety of treatments. To monitor the current outbreak, robust steps have been taken around the globe to reduce the transmission of COVID-19 infection particularly banning international and domestic flights, inducting lockdowns in vulnerable areas, social distancing etc. No clinically approved antiviral drug or vaccine against COVID-19 is reported yet. However, in clinical trials, few broad-spectrum antiviral drugs were evaluated against COVID-19 infection which resulted in clinical recovery. In this article emergence and pathogenicity of COVID-19 infection along with potential therapeutic strategies are analyzed to combat the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, the number of globally confirmed cases according to World Health Organization statistics reached 292 124 in 189 countries by 22 March 2020. The number of deaths reached 12 784, with estimated case-fatality rates ranging from 0.5% to 5.7%. Children population seems to be the least affected by the disease, while the highest rate of death is among the elderly and people with comorbidities. Most infected individuals are asymptomatic or only exhibit mild symptoms. After the incubation period, the most common symptoms are fever, cough and fatigue. Asymptomatic carrier state is of paramount importance because of carriers' ability to spread the infection and to shed the virus into the air and surroundings. Although much is still unknown about SARS-CoV-2, the scientific research is moving at an unprecedented pace towards understanding the nature, effective control, prevention and treatment of SARS-CoV-2. Various reports have suggested an in vivo evolution of the virus, which may explain the rapid spread and changing epidemiology of SARS-CoV-2, but further evidence is needed. Unfortunately, no effective treatment or therapeutic drug is available for the disease; only supportive treatment and classical intervention measures are available for confronting the SARS-CoV-2 pandemic. [ABSTRACT FROM AUTHOR]