Homology Models of Wuhan Coronavirus 3CLpro Protease

Homology Models of Coronavirus 3CLpro Protease

10.26434/chemrxiv.11637294.v2 ◽

2020 ◽

Author(s):

Martin Stoermer

Keyword(s):

Cysteine Protease ◽

Viral Genome ◽

First Generation ◽

Genomic Data ◽

Hubei Province ◽

Rapid Release ◽

Main Protease ◽

Novel Coronavirus ◽

Homology Models

A regional outbreak of pneumonia in Wuhan, Hubei Province of China in late 2019 was associated with a novel coronavirus. Rapid release of genomic data for the isolated virus enabled the construction of first-generation homology models of the new CoV 3CLpro cysteine protease. Whilst the overall viral genome was most closely associated with bat coronaviruses, the main protease is most closely related (96% identity) to SARS CoV protease.

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Homology Models of Coronavirus 2019-nCoV 3CLpro Protease

10.26434/chemrxiv.11637294 ◽

2020 ◽

Author(s):

Martin Stoermer

Keyword(s):

Cysteine Protease ◽

Viral Genome ◽

First Generation ◽

Genomic Data ◽

Hubei Province ◽

Rapid Release ◽

Main Protease ◽

Novel Coronavirus ◽

Homology Models

A regional outbreak of pneumonia in Wuhan, Hubei Province of China in late 2019 was associated with a novel coronavirus. Rapid release of genomic data for the isolated virus enabled the construction of first-generation homology models of the new CoV 3CLpro cysteine protease. Whilst the overall viral genome was most closely associated with bat coronaviruses, the main protease is most closely related (96% identity) to SARS CoV protease.

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Homology Models of Coronavirus 2019-nCoV 3CLpro Protease

10.26434/chemrxiv.11637294.v3 ◽

2020 ◽

Cited By ~ 1

Author(s):

Martin Stoermer

Keyword(s):

Cysteine Protease ◽

Viral Genome ◽

First Generation ◽

Genomic Data ◽

Hubei Province ◽

Rapid Release ◽

Main Protease ◽

Novel Coronavirus ◽

Homology Models

A regional outbreak of pneumonia in Wuhan, Hubei Province of China in late 2019 was associated with a novel coronavirus. Rapid release of genomic data for the isolated virus enabled the construction of first-generation homology models of the new CoV 3CLpro cysteine protease. Whilst the overall viral genome was most closely associated with bat coronaviruses, the main protease is most closely related (96% identity) to SARS CoV protease.

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Homology Models of the Papain-Like Protease PLpro from Coronavirus 2019-nCoV

10.26434/chemrxiv.11799705 ◽

2020 ◽

Cited By ~ 1

Author(s):

Martin Stoermer

Keyword(s):

Viral Genome ◽

Public Health Emergency ◽

World Health ◽

Rapid Spread ◽

The World ◽

Novel Coronavirus ◽

Health Organization ◽

3Cl Protease ◽

Bat Coronavirus ◽

Homology Models

The December 2019 outbreak of pneumonia in Wuhan, Hubei Province of China was rapidly linked to a novel coronavirus 2019-nCoV. The rapid spread and severity of the virus has led the World Health Organization to declare it a Public Health Emergency of International Concern. We recently described the first homology models of the main 3CL protease from 2019-nCoV, and now present models of the other viral protease, the papain-like protease or PLpro. Whilst the overall viral genome is most closely associated with bat coronaviruses, no bat PLpro crystal structures are known. Wuhan 2019-nCoV PLpro is most closely related to a bat coronavirus PLpro (97% identity), then SARS (80 %) and MERS (29%) and the most promising models presented here are prepared from SARS crystal structure templates.

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Homology Models of the Papain-Like Protease PLpro from Coronavirus 2019-nCoV

10.26434/chemrxiv.11799705.v1 ◽

2020 ◽

Cited By ~ 2

Author(s):

Martin Stoermer

Keyword(s):

Viral Genome ◽

Public Health Emergency ◽

World Health ◽

Rapid Spread ◽

The World ◽

Novel Coronavirus ◽

Health Organization ◽

3Cl Protease ◽

Bat Coronavirus ◽

Homology Models

The December 2019 outbreak of pneumonia in Wuhan, Hubei Province of China was rapidly linked to a novel coronavirus 2019-nCoV. The rapid spread and severity of the virus has led the World Health Organization to declare it a Public Health Emergency of International Concern. We recently described the first homology models of the main 3CL protease from 2019-nCoV, and now present models of the other viral protease, the papain-like protease or PLpro. Whilst the overall viral genome is most closely associated with bat coronaviruses, no bat PLpro crystal structures are known. Wuhan 2019-nCoV PLpro is most closely related to a bat coronavirus PLpro (97% identity), then SARS (80 %) and MERS (29%) and the most promising models presented here are prepared from SARS crystal structure templates.

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Drug Repurposing Studies Targeting SARS-nCoV2: An Ensemble Docking Approach on Drug Target 3C-like Protease (3CLpro)

10.26434/chemrxiv.12228831 ◽

2020 ◽

Author(s):

Shruti Koulgi ◽

Vinod Jani ◽

Mallikarjunachari Uppuladinne ◽

Uddhavesh Sonavane ◽

Asheet Kumar Nath ◽

...

Keyword(s):

Drug Repurposing ◽

Drug Binding ◽

Ensemble Docking ◽

Drug Molecules ◽

Drug Binding Site ◽

Main Protease ◽

Docking Approach ◽

Novel Coronavirus ◽

Markov State Modeling ◽

Viral Polyprotein

The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-nCoV2). SARS-nCoV2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-03. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-nCoV2. The high-resolution crystal structure of 3CLpro (main protease) of SARS-nCoV2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration (FDA) approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for main protease helped in exploring the conformational variation in the drug binding site of the main protease leading to efficient binding of more relevant drug molecules. The drugs obtained as best hits from the ensemble docking possessed anti-bacterial and anti-viral properties. Small molecules with these properties may prove to be useful to treat symptoms exhibited in COVID-19. This in-silico ensemble docking approach would support identification of potential candidates for repurposing against COVID-19.

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Comparative docking of SARS-CoV-2 receptors antagonists from repurposing drugs

10.26434/chemrxiv.12044538.v4 ◽

2020 ◽

Author(s):

Micael Davi Lima de Oliveira ◽

Kelson Mota Teixeira de Oliveira

Keyword(s):

World Health Organisation ◽

World Health ◽

Lung Cells ◽

The Novel ◽

High Modulation ◽

Main Protease ◽

The World ◽

Novel Coronavirus ◽

Viral Receptors ◽

Theoretical Results

According to the World Health Organisation, until 16 June, 2020, the number of confirmed and notified cases of COVID-19 has already exceeded 7.9 million with approximately 434 thousand deaths worldwide. This research aimed to find repurposing antagonists, that may inhibit the activity of the main protease (Mpro) of the SARS-CoV-2 virus, as well as partially modulate the ACE2 receptors largely found in lung cells, and reduce viral replication by inhibiting Nsp12 RNA polymerase. Docking molecular simulations were performed among a total of 60 structures, most of all, published in the literature against the novel coronavirus. The theoretical results indicated that, in comparative terms, paritaprevir, ivermectin, ledipasvir, and simeprevir, are among the most theoretical promising drugs in remission of symptoms from the disease. Furthermore, also corroborate indinavir to the high modulation in viral receptors. The second group of promising drugs includes remdesivir and azithromycin. The repurposing drugs HCQ and chloroquine were not effective in comparative terms to other drugs, as monotherapies, against SARS-CoV-2 infection.

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Current updates on COVID-19 - A review

International Journal of Novel Trends in Pharmaceutical Sciences ◽

10.26452/ijntps.v10i1.1141 ◽

2020 ◽

Vol 10 (1) ◽

pp. 1-8

Author(s):

Ghotekar D S ◽

Vishal N Kushare ◽

Sagar V Ghotekar

Keyword(s):

World Health Organization ◽

Common Cold ◽

Respiratory Diseases ◽

Gastrointestinal Diseases ◽

Hubei Province ◽

World Health ◽

The World ◽

The Common ◽

Novel Coronavirus ◽

Health Organization

Coronaviruses are a family of viruses that cause illness such as respiratory diseases or gastrointestinal diseases. Respiratory diseases can range from the common cold to more severe diseases. A novel coronavirus outbreak was first documented in Wuhan, Hubei Province, China in December 2019. The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) a pandemic. A global coordinated effort is needed to stop the further spread of the virus. A novel coronavirus (nCoV) is a new strain that has not been identified in humans previously. Once scientists determine exactly what coronavirus it is, they give it a name (as in the case of COVID-19, the virus causing it is SARS-CoV-2).

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