scholarly journals Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products

2020 ◽  
Vol 12 (3) ◽  
pp. 335-348 ◽  
Author(s):  
Abbas Khan ◽  
Mazhar Khan ◽  
Shoaib Saleem ◽  
Zainib Babar ◽  
Arif Ali ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Natural Products ◽  
Rna Polymerase ◽  
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 Phylogenetic analysis of the RNA-dependent RNA polymerase (RdRp) and a predicted structural protein (pSP) of the Chronic bee paralysis virus (CBPV) isolated from various geographic regions

2009 ◽  
Vol 144 (1-2) ◽  
pp. 334-338 ◽  
Author(s):  
Philippe Blanchard ◽  
Frank Schurr ◽  
Violaine Olivier ◽  
Olivier Celle ◽  
Karina Antùnez ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Rna Polymerase ◽  
Structural Protein ◽  
Rna Dependent Rna Polymerase ◽  
Geographic Regions ◽  
Paralysis Virus

scholarly journals In Silico Discovery of Natural Products Against Dengue RNA-Dependent RNA Polymerase Drug Target

2021 ◽  
Vol 21 (0) ◽  
pp. 11-27
Author(s):  
Junie B. Billones ◽  
Nina Abigail B. Clavio
Keyword(s):  
Natural Products ◽  
Rna Polymerase ◽  
In Silico ◽  
Drug Target ◽  
Rna Dependent Rna Polymerase

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 Molecular Characterization of a Novel Ourmia-Like Virus Infecting Phoma matteucciicola

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 231 ◽  
Author(s):  
Jia Zhou ◽  
Yuhua Wang ◽  
Xiaofei Liang ◽  
Changping Xie ◽  
Wenbo Liu ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Rna Polymerase ◽  
Molecular Characterization ◽  
Open Reading Frame ◽  
Single Open Reading Frame ◽  
Rna Dependent Rna Polymerase ◽  
Reading Frame ◽  
The Family

Here, we report a novel (+) ssRNA mycovirus, Phoma matteucciicola ourmia-like virus 1 (PmOLV1), isolated from Phoma matteucciicola strain LG915-1. The genome of PmOLV1 was 2603 nucleotides long and contained a single open reading frame (ORF), which could be translated into a product of RNA-dependent RNA polymerase (RdRp) by both standard and mitochondrial genetic codons. Cellular fractionation assay indicated that PmOLV1 RNAs are likely more enriched in mitochondria than in cytoplasm. Phylogenetic analysis indicated that PmOLV1 is a new member of the genus Penoulivirus (recently proposed) within the family Botourmiaviridae.

scholarly journals Genetic variability and phylogenetic analysis of Lagovirus europaeus strains GI.1 (RHDV) and GI.2 (RHDV2) based on the RNA-dependent RNA polymerase (RdRp) coding gene

2020 ◽  
Author(s):  
Beata Hukowska-Szematowicz
Keyword(s):  
Phylogenetic Analysis ◽  
Genetic Variability ◽  
Rna Polymerase ◽  
Genetic Distance ◽  
Disease Virus ◽  
Genetic Material ◽  
Rabbit Haemorrhagic Disease Virus ◽  
Rna Dependent Rna Polymerase ◽  
Rabbit Haemorrhagic Disease ◽  
Haemorrhagic Disease

Lagovirus europaeus GI.1 (RHDV-rabbit haemorrhagic disease virus) and GI.2 (RHDV2-rabbit haemorrhagic disease virus 2), family Caliciviridae, genus Lagovirus, are etiological factors of the rabbit haemorrhagic disease (RHD). This small RNA virus is a great model for tracking the variability and evolution of RNA viruses, because it uses an RNA-dependent RNA polymerase (RdRp) to replicate its own genetic material. This polymerase determines the fidelity and the rates of replication and mutation of the virus, conditioning its adaptation to the environment and even to a new host, and thus influencing evolution of the virus. The aim of this study was to determine the genetic variability and phylogenetic relationships of 105 Lagovirus europaeus strains with different genotypes based on the RdRp gene. The strains came from around the world in the years of 1987–2017. The aforementioned group of 105 strains included 14 strains whose RdRp sequences were obtained and analysed in this study, and the rest were retrieved from GenBank: 74 strains classified as genotype GI.1 (RHDV), 14 as GI.2 (RHDV2), 2 strains of Lagovirus europaeus not assigned to any genotype, and a MRCV strain, the sequences of which were collected from GenBank. Among the 14 strains whose RdRp sequences were obtained in this study, the highest variability was presented in the Austrian 237 strain from 2004. The genetic distance between the Austrian 237 strain and the remaining thirteen analysed strains ranged from 0.117 to 0.123 (from 11.7% to 12.3% nucleotide substitutions). The lowest variability, however, was recorded for Hungarian, Czech and Austrian strains. On the phylogenetic tree, the 14 analysed strains were allocated into GI.1c (G2), GI.1d (G3-G5) and GI.1a (RHDVa). Analysis of the genetic variability of the 105 strains of Lagovirus europaeus indicated a growing genetic distance between the strains, both in time and location. Phylogenetic analysis showed a division of the strains into seven groups, dictated by the chronology, geographical location and evolutionary events in the history of the virus, such as mutations and recombinations.

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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