Identifying Therapeutic Compounds Targeting RNA-Dependent-RNA-Polymerase of Sars-Cov-2

Universal Force Field ◽

Medicinal Use ◽

Force Field Analysis ◽

Antiviral Activities ◽

Low Toxicity ◽

COVID-19 emerged as the biggest threat of this century for mankind and later it spread across the globe through human to human transmission. Scientists rushed to understand the structure and mechanism of the virus so that antiviral drugs or vaccines to control this disease can be developed. A key to stop the progression of the disease is to inhibit the replication mechanism of Sars-Cov-2. RNA-dependent-RNA polymerase protein also called RdRp protein is the engine of Sars-Cov-2 that replicates the virus using viral RNA when it gains entry into the human cell. Numerous drugs proposed for the treatment of COVID-19 such as Camostat Mesylate, Remdesivir, Famotidine, Hesperidin, etc. are under trial to analyze the aftermath of their medicinal use. Nature is enriched with compounds that have antiviral activities and can potentially play a pivotal role to inhibit this virus. This study focuses on the phytochemicals that have the potential to exhibit antiviral activities. A large number of compounds were screened and a cohort of most suitable ones are suggested via in-silico techniques which are used worldwide for drug discovery such as docking, binding analysis, Universal Force Field Analysis, Broyden-Fletcher-Goldfarb-Shanno (BFGS) Method, Molecular Dynamic Simulation, and Electrostatic Potential Calculation. The proposed compounds are naturally occurring substances with low toxicity, very few side effects, proven anti-pathogenic effects, and most importantly are easily available.

Identifying Therapeutic Compounds Targeting RNA-Dependent-RNA-Polymerase of Sars-Cov-2

10.26434/chemrxiv.12477761.v2 ◽

2020 ◽

Author(s):

Muhammad Roomi ◽

Muhammad Mahmood ◽

Yaser Khan

Keyword(s):

Rna Polymerase ◽

Field Analysis ◽

Universal Force Field ◽

Medicinal Use ◽

Force Field Analysis ◽

Antiviral Activities ◽

Low Toxicity ◽

COVID-19 emerged as the biggest threat of this century for mankind and later it spread across the globe through human to human transmission. Scientists rushed to understand the structure and mechanism of the virus so that antiviral drugs or vaccines to control this disease can be developed. A key to stop the progression of the disease is to inhibit the replication mechanism of Sars-Cov-2. RNA-dependent-RNA polymerase protein also called RdRp protein is the engine of Sars-Cov-2 that replicates the virus using viral RNA when it gains entry into the human cell. Numerous drugs proposed for the treatment of COVID-19 such as Camostat Mesylate, Remdesivir, Famotidine, Hesperidin, etc. are under trial to analyze the aftermath of their medicinal use. Nature is enriched with compounds that have antiviral activities and can potentially play a pivotal role to inhibit this virus. This study focuses on the phytochemicals that have the potential to exhibit antiviral activities. A large number of compounds were screened and a cohort of most suitable ones are suggested via in-silico techniques which are used worldwide for drug discovery such as docking, binding analysis, Universal Force Field Analysis, Broyden-Fletcher-Goldfarb-Shanno (BFGS) Method, Molecular Dynamic Simulation, and Electrostatic Potential Calculation. The proposed compounds are naturally occurring substances with low toxicity, very few side effects, proven anti-pathogenic effects, and most importantly are easily available.

Identifying Therapeutic Compounds Targeting RNA-Dependent-RNA-Polymerase of Sars-Cov-2

10.26434/chemrxiv.12477761.v3 ◽

2020 ◽

Cited By ~ 1

Author(s):

Muhammad Roomi ◽

Muhammad Mahmood ◽

Yaser Khan

Keyword(s):

Rna Polymerase ◽

Field Analysis ◽

Universal Force Field ◽

Medicinal Use ◽

Force Field Analysis ◽

Antiviral Activities ◽

Low Toxicity ◽

COVID-19 emerged as the biggest threat of this century for mankind and later it spread across the globe through human to human transmission. Scientists rushed to understand the structure and mechanism of the virus so that antiviral drugs or vaccines to control this disease can be developed. A key to stop the progression of the disease is to inhibit the replication mechanism of Sars-Cov-2. RNA-dependent-RNA polymerase protein also called RdRp protein is the engine of Sars-Cov-2 that replicates the virus using viral RNA when it gains entry into the human cell. Numerous drugs proposed for the treatment of COVID-19 such as Camostat Mesylate, Remdesivir, Famotidine, Hesperidin, etc. are under trial to analyze the aftermath of their medicinal use. Nature is enriched with compounds that have antiviral activities and can potentially play a pivotal role to inhibit this virus. This study focuses on the phytochemicals that have the potential to exhibit antiviral activities. A large number of compounds were screened and a cohort of most suitable ones are suggested via in-silico techniques which are used worldwide for drug discovery such as docking, binding analysis, Universal Force Field Analysis, Broyden-Fletcher-Goldfarb-Shanno (BFGS) Method, Molecular Dynamic Simulation, and Electrostatic Potential Calculation. The proposed compounds are naturally occurring substances with low toxicity, very few side effects, proven anti-pathogenic effects, and most importantly are easily available.

Identifying Therapeutic Compounds Targeting RNA-Dependent-RNA-Polymerase of Sars-Cov-2

10.26434/chemrxiv.12477761 ◽

2020 ◽

Author(s):

Muhammad Roomi ◽

Muhammad Mahmood ◽

Yaser Khan

Keyword(s):

Rna Polymerase ◽

Field Analysis ◽

Universal Force Field ◽

Medicinal Use ◽

Force Field Analysis ◽

Antiviral Activities ◽

Low Toxicity ◽

COVID-19 emerged as the biggest threat of this century for mankind and later it spread across the globe through human to human transmission. Scientists rushed to understand the structure and mechanism of the virus so that antiviral drugs or vaccines to control this disease can be developed. A key to stop the progression of the disease is to inhibit the replication mechanism of Sars-Cov-2. RNA-dependent-RNA polymerase protein also called RdRp protein is the engine of Sars-Cov-2 that replicates the virus using viral RNA when it gains entry into the human cell. Numerous drugs proposed for the treatment of COVID-19 such as Camostat Mesylate, Remdesivir, Famotidine, Hesperidin, etc. are under trial to analyze the aftermath of their medicinal use. Nature is enriched with compounds that have antiviral activities and can potentially play a pivotal role to inhibit this virus. This study focuses on the phytochemicals that have the potential to exhibit antiviral activities. A large number of compounds were screened and a cohort of most suitable ones are suggested via in-silico techniques which are used worldwide for drug discovery such as docking, binding analysis, Universal Force Field Analysis, Broyden-Fletcher-Goldfarb-Shanno (BFGS) Method, Molecular Dynamic Simulation, and Electrostatic Potential Calculation. The proposed compounds are naturally occurring substances with low toxicity, very few side effects, proven anti-pathogenic effects, and most importantly are easily available.

Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism

10.1101/2020.03.24.992230 ◽

2020 ◽

Author(s):

Qi Liu ◽

Amita Gupta ◽

Ayse Okesli-Armlovich ◽

Wenjie Qiao ◽

Curt R. Fischer ◽

...

Keyword(s):

Rna Polymerase ◽

Antiviral Agent ◽

Dihydroorotate Dehydrogenase ◽

New Host ◽

Genome Wide ◽

Pyrimidine Salvage ◽

Antiviral Activities ◽

Salvage Pathways ◽

Targeting Strategy

AbstractGenome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase (DHODH) as its target, along with the discovery that knockdown of genes in pyrimidine salvage pathways sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was efficiently converted into its triphosphates in cells. When combined with GSK983, it led to large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral genome infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activities of RdRp inhibitors.

Starting Anti-COVID-19 Drug Discovery with Natural Products

Fronteiras Journal of Social Technological and Environmental Science ◽

10.21664/2238-8869.2021v10i1.p241-270 ◽

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 ◽

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.