TY - JOUR
T1 - Drug repositioning to target NSP15 protein on SARS-CoV-2 as possible COVID-19 treatment
AU - Sixto-López, Yudibeth
AU - Martínez-Archundia, Marlet
N1 - Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2021/5/15
Y1 - 2021/5/15
N2 - SARS-CoV and SARS-CoV-2 belong to the subfamily Coronaviridae and infect humans, they are constituted by four structural proteins: Spike glycoprotein (S), membrane (M), envelope (E) and nucleocapsid (N), and nonstructural proteins, such as Nsp15 protein which is exclusively present on nidoviruses and is absent in other RNA viruses, making it an ideal target in the field of drug design. A virtual screening strategy to search for potential drugs was proposed, using molecular docking to explore a library of approved drugs available in the DrugBank database in order to identify possible NSP15 inhibitors to treat Covid19 disease. We found from the docking analysis that the antiviral drugs: Paritaprevir and Elbasvir, currently both approved for hepatitis C treatment which showed some of the lowest free binding energy values were considered as repositioning drugs to combat SARS-CoV-2. Furthermore, molecular dynamics simulations of the Apo and Holo-Nsp15 systems were performed in order to get insights about the stability of these protein-ligand complexes.
AB - SARS-CoV and SARS-CoV-2 belong to the subfamily Coronaviridae and infect humans, they are constituted by four structural proteins: Spike glycoprotein (S), membrane (M), envelope (E) and nucleocapsid (N), and nonstructural proteins, such as Nsp15 protein which is exclusively present on nidoviruses and is absent in other RNA viruses, making it an ideal target in the field of drug design. A virtual screening strategy to search for potential drugs was proposed, using molecular docking to explore a library of approved drugs available in the DrugBank database in order to identify possible NSP15 inhibitors to treat Covid19 disease. We found from the docking analysis that the antiviral drugs: Paritaprevir and Elbasvir, currently both approved for hepatitis C treatment which showed some of the lowest free binding energy values were considered as repositioning drugs to combat SARS-CoV-2. Furthermore, molecular dynamics simulations of the Apo and Holo-Nsp15 systems were performed in order to get insights about the stability of these protein-ligand complexes.
KW - COVID-19
KW - Elbasvir
KW - Nsp15
KW - Paritaprevir
KW - SARS-CoV-2
KW - molecular dynamic simulation
UR - http://www.scopus.com/inward/record.url?scp=85102575271&partnerID=8YFLogxK
U2 - 10.1002/jcc.26512
DO - 10.1002/jcc.26512
M3 - Artículo
C2 - 33713492
AN - SCOPUS:85102575271
SN - 0192-8651
VL - 42
SP - 897
EP - 907
JO - Journal of Computational Chemistry
JF - Journal of Computational Chemistry
IS - 13
ER -