scholarly journals Peer Review #1 of "Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase (v0.1)"

2020 ◽  
Keyword(s):  
Natural Products ◽  
Rna Polymerase ◽  
Peer Review ◽  
Rna Dependent Rna Polymerase

scholarly journals Computationally repurposed drugs and natural products against RNA dependent RNA polymerase as potential COVID-19 therapies

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Sakshi Piplani ◽  
Puneet Kumar Singh ◽  
David A. Winkler ◽  
Nikolai Petrovsky
Keyword(s):  
Natural Products ◽  
Rna Polymerase ◽  
Kinase Inhibitor ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Rna Dependent Rna Polymerase ◽  
Starting Point ◽  
Potential Activity ◽  
Repurposed Drugs ◽  
Multiple Drugs

AbstractRepurposing of existing drugs and drug candidates is an ideal approach to identify new potential therapies for SARS-CoV-2 that can be tested without delay in human trials of infected patients. Here we applied a virtual screening approach using Autodock Vina and molecular dynamics simulation in tandem to calculate binding energies for repurposed drugs against the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). We thereby identified 80 promising compounds with potential activity against SARS-Cov2, consisting of a mixture of antiviral drugs, natural products and drugs with diverse modes of action. A substantial proportion of the top 80 compounds identified in this study had been shown by others to have SARS-CoV-2 antiviral effects in vitro or in vivo, thereby validating our approach. Amongst our top hits not previously reported to have SARS-CoV-2 activity, were eribulin, a macrocyclic ketone analogue of the marine compound halichondrin B and an anticancer drug, the AXL receptor tyrosine kinase inhibitor bemcentinib. Our top hits from our RdRp drug screen may not only have utility in treating COVID-19 but may provide a useful starting point for therapeutics against other coronaviruses. Hence, our modelling approach successfully identified multiple drugs with potential activity against SARS-CoV-2 RdRp.

scholarly journals Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10480
Author(s):  
Mahmoud Kandeel ◽  
Yukio Kitade ◽  
Abdullah Almubarak
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Rna Polymerase ◽  
Screening Assay ◽  
Rna Dependent Rna Polymerase ◽  
Recent Emergence ◽  
Essential Enzyme ◽  
Approved Drugs ◽  
Dynamics Simulations ◽  
Fda Approved Drugs

Following the recent emergence of SARS-CoV-2 or coronavirus disease 2019 (COVID-19), drug discovery and vaccine design to combat this fatal infection are critical. In this study, an essential enzyme in the SARS-CoV-2 replication machinery, RNA-dependent RNA polymerase (RDRP), is targeted in a virtual screening assay using a set of 1,664 FDA-approved drugs, including sets of botanical and synthetic derivatives. A set of 22 drugs showed a high docking score of >−7. Notably, approximately one-third of the top hits were either from natural products or biological molecules. The FDA-approved phytochemicals were sennosides, digoxin, asiaticoside, glycyrrhizin, neohesperidin, taxifolin, quercetin and aloin. These approved natural products and phytochemicals are used as general tonics, antioxidants, cell protectives, and immune stimulants (nadid, thymopentin, asiaticoside, glycyrrhizin) and in other miscellaneous systemic or topical applications. A comprehensive analysis was conducted on standard precision and extra precision docking, two-step molecular dynamics simulations, binding energy calculations and a post dynamics analysis. The results reveal that two drugs, docetaxel and neohesperidin, showed strong binding profiles with SARS CoV-2 RdRP. These results can be used as a primer for further drug discovery studies in the treatment of COVID-19. This initiative repurposes safe FDA-approved drugs against COVID-19 RdRP, providing a rapid channel for the discovery and application of new anti-CoV therapeutics.

scholarly journals Starting Anti-COVID-19 Drug Discovery with Natural Products

2021 ◽  
Vol 10 (1) ◽  
pp. 241-270
Author(s):  
OSMAR NASCIMENTO SILVA ◽  
Bruno Neves ◽  
Lucimar Rosseto ◽  
Rodrigo Moura ◽  
Hamilton Napolitano ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Rna Polymerase ◽  
Pegylated Interferon ◽  
Rna Dependent Rna Polymerase ◽  
Antiviral Effects ◽  
Frequent Mutations ◽  
Antiviral Activities ◽  
Underlying Mechanisms ◽  
High Infectivity

COVID-19 was characterized as a pandemic regarding its rapid international spread and severity on March 2020. The Coronaviridae family receives this name regarding the organization of the spike glycoprotein located in the envelope, which resembles a stellar corona when observed under a microscope. Coronaviruses undergo frequent mutations in their genome due to errors made by RNA-dependent RNA polymerase (RdRp). The SARS-CoV-2 was characterized by high infectivity and person to person transmission, with an incubation period of up to fourteen days. Potent antiviral activities of several natural products such as alkaloids, chalcones, triterpenoids have been reported but with unconfirmed efficacy or safety in the clinic as well as the complete underlying mechanisms. Also, CQ, HCQ and Ivermectin, remdesivir, lopinavir, ritonavir, favipiravir and pegylated interferon with ribavirin have been tested to develop both an effective therapy and a vaccine to treat COVID-19.  This study presents the antiviral effects of the natural products against SARS-CoV, HCoV-NL63, HCoV-229E and HCoV-OC43 showing that Lycorine, Emodin, Promazine, Saikosaponins B2, Silvestrol, Cepharanthine, Fangchinoline, Tetrandrine, Caffeic acid, Chlorogenic acid, Gallic acid and Emetine are a good candidates on treatment of coronaviruses infections.

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