In silico-based studies on phytochemicals from native Indian plants as potential inhibitors of SARS-CoV-2

This study aims to analyze the AntiCovid effect of Phytocompounds extracted from Native Indian Plant species by computational methods such as Molecular Docking. Through this study keeping the Indian Heritage alive we characterized the ability of these phytochemicals as inhibiting agents of the Main Protease enzyme of this Virus. The lack of any effective treatment and the reoccurrence of cases despite Vaccination necessitates the quick provision of anti-SARS-CoV-2 drugs. Natural substances are getting a lot of attention for SARS-CoV-2 therapy as they have proven antimicrobial activities and are a key source for numerous antiviral drugs. Despite the fact that this virus has several identified target receptors, Main Protease (Mpro) is crucial for viral replication. In this study, 26 phytochemicals from 10 native Indian plant species were studied. Our docking studies demonstrated that compounds Quercetin, Withaferin A, Sominone, and Nimbin were likely to be more favorable than the natural inhibitor N3, with binding energies of?8.42, ?9.21, ?9.95, and ?8.88 kcal/mol, respectively. These four candidate natural compounds were further examined for their bioavailability scoresthrough ADMET analysis to prove the safety of these compounds as well as their drug likeliness.Through the results it was indicated that these natural phytochemicals have a significant potential of inhibiting the SARS-CoV-2 Mpro enzyme and might be utilized to treat SARS-CoV-2 and manage public health, subject to in vitro validation in the future.

Advances in peptidomimetic inhibitors of coronavirus main protease / 药学学报

Coronavirus (CoVs) is a widespread pathogen that can infect humans and animals to cause serious acute and chronic respiratory diseases. Among them, SARS-CoV broke out in 2003, MERS-CoV was discovered and spread widely in 2012, and SARS-CoV-2 emerged at the end of 2019. They all belong to β-coronavirus. Peptidomimetic inhibitors targeting coronavirus main proteases (Mpro, 3CLpro) have attracted much attention because of their broad spectrum and strong antiviral efficacy. In this review, peptidomimetic inhibitors of coronavirus main protease were classified and summarized according to the different "warheads" in design strategy. And also, the molecular structures, biological activity and design ideas of the inhibitors were analyzed and discussed, which is aimed to provide useful reference for further design and development of coronavirus inhibitors.

Should COVID-19 be branded to viral thrombotic fever?

Coronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing coronavirus disease 2019 (COVID-19). Over one year's time period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID-19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to viral haemorrhagic fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a viral thrombotic fever. This manuscript points out that SARS-CoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a "thrombotic storm," much more than a "cytokine storm." The importance of a viral protease called main protease (Mpro) is highlighted as a critical component for its replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison crystallographic structures.

Molecular Docking Of Selected Bioactive Compounds From Azadirachta Indica For The Inhibition Of Covid19 Protease

Objective: COVID-19 caused by novel SARS-coronavirus 2 belonging to family Coronaviridae, is a global public health emergency infecting many people all around the world, especially in India with more than 2,98,000 cases. Hence there is a need for a novel drug that counters SARS-CoV2 is the prime requirement at this time. Methods: The present study aimed to assess bioactive compounds found in Azadirachta indica as a potential inhibitor of COVID-19 Mpr °(6Y2E, 6LU7, and 2GTB) by Autodock 4.2, with the Lamarckian Genetic Algorithm. COVID-19 Mpr ° was docked with thirteen bioactive compounds, and docking was analyzed by Autodock 4.2 and Pymol. Nelfinavir and Saquinavir were used as positive standards for comparison. Results: Azadirachtanin, Azadirachtol, and Salannolide, were left out because of the violation of Lipinski’s rule. The binding energies obtained from the docking of 6Y2E with a native ligand, Azadiradione, Beta-sitosterol, Epiazadiradione, Epoxyazadiradione, Kaempferol, Meldenin, Myricetin, Nimbaflavone, Nimbinene, Nimbione, Nimbocinolide, Quercitrin, Vepnin, Saquinavir, and Nelfinavir were-7.32,-6.63,-6.69,-7.52,-5.27,-4.54,-6.07,-4.19,-5.02,-5.58,-6.23,-4.71, -3.72,-6.4,-7.14 and-4.67 kcal/mol respectively. The binding energies obtained from the docking of 6LU7 with the native ligand, Azadiradione, Nimbione, Vepnin, and Saquinavir were-6.14,-6.48,-6.79 and-6.49 kcal/mol correspondingly. The binding energies obtained from the docking of 2GTB with the native ligand, Azadiradione, Epiazadiradione, Epoxyazadiradione, Kaempferol, Meldenin, Myricetin, Nimbaflavone, Nimbione, Nimbocinolide, Quercitrin, Vepnin, Saquinavir, and Nelfinavir were-6.96,-7.13,-6.69,-5.22,-6.44,-5.06,-5.93,-6.66,-5.3,-5.63,-7.11,-6.89 and-5.42kcal/mol, respectively. Conclusion: Azadiradione, Epiazadiradione, Nimbione, and Vepnin seemed to have the greatest potential to act as COVID-19 protease inhibitors. However, further research is necessary to explore their prospective medicinal use in vitro and in vivo conditions.

Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase / 药物分析学报

Recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health safety. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are under way to test possible therapies. During this urgent situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated the highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach has facilitated the identifi-cation of potential binding modes and favourable molecular interaction profile of corresponding com-pounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural infor-mation obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.

Coagulation modifiers targeting SARS-CoV-2 main protease Mpro for COVID-19 treatment: an in silico approach

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection depends on viral polyprotein processing, catalysed by the main proteinase (Mpro). The solution of the SARS-CoV-2 Mpro structure allowed the investigation of potential inhibitors. This work aims to provide first evidences of the applicability of commercially approved drugs to treat coronavirus disease-19 (COVID-19). We screened 4,334 compounds to found potential inhibitors of SARS-CoV-2 replication using an in silico approach. Our results evidenced the potential use of coagulation modifiers in COVID-19 treatment due to the structural similarity of SARS-CoV-2 Mpro and human coagulation factors thrombin and Factor Xa. Further in vitro and in vivo analysis are needed to corroborate these results.