RESEARCH: COVID-19
FOLDING PROJECT #16515 PROFILE

This project uses computer simulations to study how certain drugs might stop the SARS-CoV-2 virus from replicating. They focus on proteins nsp12 and nsp14, which are important for viral replication. The project tests different drug candidates, including Ribavirin and analogs, to see if they can block these proteins and stop the virus.

This series of CPU projects to simulation the Nonstructural protein 12 (nsp12) and Nonstructural protein 14 (nsp14) complexes.

We will screen existing FDA-approved NTP analog drugs (e.g.

Ribirine).

We aim to repurpose drugs that can inhibit SARS-CoV-2 replication 16500: This project contains simulations of nsp14-ExoN and nsp10 of the SARS-CoV-2 in complex with a short nascent RNA.

Nsp14 is in charge of proofeading of the replication SARS-CoV-2 by removing mis-incoproated nucleotides including drugs, so that it is important that NTP analog drugs (e.g.

Remdesivir) added to the nascent RNA do not get cleaved by nsp14. 16501: This project contains simulations of nsp12, nsp7, and nsp8 of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA, and Ribavirin Triphosphate in the active site.

We aim to examine if the drug Ribirine can inhibite the viral replicaiton of SARS-CoV-2. 16502: This project contains simulations of nsp12, nsp7 and nsp8 of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA with Ribavirin as the 3’ terminal nucleotide. 16503: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA and Cladribine Triphosphate in the active site. 16504: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA and Clofarabine Triphosphate in the active site. 16505: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA and Cordycepin Triphosphate in the active site.

16506: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA(Cladribine at 3'-terminal), and ATP in the active site.

16507: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA(Clofarabine at 3'-terminal), and ATP in the active site. 16508: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA(Cordycepin at 3'-terminal), and ATP in the active site. 16509: Nonstructural protein 14 and 10 (nsp14-ExoN & nsp 10) of the SARS-CoV-2 in complex with a short nascent RNA containing Cordycepin at 3'-terminal. 16510: Nonstructural protein 14 and 10 (nsp14-ExoN & nsp 10) of the SARS-CoV-2 in complex with a short nascent RNA containing Clofarabine at 3'-terminal. 16513: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA, and ATP in the active site. 16514: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA, and GTP in the active site. 16515: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA, and GTP in the active site with nonbonded dummy ion model. 16516: Nonstructural protein 12 (nsp12-RdRp & nsp7 & nsp8) of the SARS-CoV-2 in complex with the RNA template, a short nascent RNA, and ATP in the active site with nonbonded dummy ion model.

Nonstructural protein 12

A viral protein involved in RNA replication.

Nonstructural protein 12 (nsp12) is a crucial component of the SARS-CoV-2 virus, responsible for replicating its RNA genome. It plays a vital role in the virus's ability to infect cells and spread.

Nonstructural protein 14

A viral protein that acts as a proofreader during RNA replication.

Nonstructural protein 14 (nsp14) helps ensure the accuracy of the SARS-CoV-2 virus's RNA genome by removing errors made during replication. This 'proofreading' function is essential for the virus to produce functional copies of its genetic material.

FDA

Food and Drug Administration

The FDA is a US government agency responsible for regulating food, drugs, cosmetics, and medical devices. It plays a crucial role in ensuring the safety and efficacy of these products.

NTP analog

A molecule structurally similar to nucleoside triphosphates (NTPs), used as antiviral drugs.

NTP analogs are synthetic molecules designed to resemble the building blocks of viral RNA. They interfere with viral replication by acting as false nucleotides, preventing the virus from making new copies of its genetic material.

Remdesivir

An antiviral medication used to treat COVID-19.

Remdesivir is an intravenous antiviral drug that has been shown to shorten the recovery time for hospitalized patients with severe COVID-19. It works by inhibiting the activity of the SARS-CoV-2 virus's RNA polymerase, preventing it from replicating its genetic material.

SARS-CoV-2

The virus responsible for the COVID-19 pandemic.

SARS-CoV-2 is a novel coronavirus that emerged in late 2019, causing the global COVID-19 pandemic. It spreads primarily through respiratory droplets and can lead to a range of symptoms from mild cold-like illness to severe pneumonia and death.

Ribonucleoside Triphosphate

Nucleotides that serve as building blocks for RNA synthesis.

Ribonucleoside triphosphates (NTPs) are essential molecules involved in the process of RNA synthesis. They provide the individual nucleotide units that are linked together to form RNA chains, ultimately coding for proteins and regulating cellular functions.