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http://dx.doi.org/10.5808/gi.21040

Microsecond molecular dynamics simulations revealed the inhibitory potency of amiloride analogs against SARS-CoV-2 E viroporin  

Jaber, Abdullah All (Department of Biochemistry and Microbiology, North South University)
Chowdhury, Zeshan Mahmud (Department of Biochemistry and Microbiology, North South University)
Bhattacharjee, Arittra (Department of Biochemistry and Microbiology, North South University)
Mourin, Muntahi (Department of Microbiology, University of Manitoba)
Keya, Chaman Ara (Department of Biochemistry and Microbiology, North South University)
Bhuyan, Zaied Ahmed (Department of Biochemistry and Microbiology, North South University)
Publication Information
Genomics & Informatics / v.19, no.4, 2021 , pp. 48.1-48.10 More about this Journal
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes small envelope protein (E) that plays a major role in viral assembly, release, pathogenesis, and host inflammation. Previous studies demonstrated that pyrazine ring containing amiloride analogs inhibit this protein in different types of coronavirus including SARS-CoV-1 small envelope protein E (SARS-CoV-1 E). SARS-CoV-1 E has 93.42% sequence identity with SARS-CoV-2 E and shared a conserved domain NS3/small envelope protein (NS3_envE). Amiloride analog hexamethylene amiloride (HMA) can inhibit SARS-CoV-1 E. Therefore, we performed molecular docking and dynamics simulations to explore whether amiloride analogs are effective in inhibiting SARS-CoV-2 E. To do so, SARS-CoV-1 E and SARS-CoV-2 E proteins were taken as receptors while HMA and 3-amino-5-(azepan-1-yl)-N-(diaminomethylidene)-6-pyrimidin-5-ylpyrazine-2-carboxamide (3A5NP2C) were selected as ligands. Molecular docking simulation showed higher binding affinity scores of HMA and 3A5NP2C for SARS-CoV-2 E than SARS-CoV-1 E. Moreover, HMA and 3A5NP2C engaged more amino acids in SARS-CoV-2 E. Molecular dynamics simulation for 1 ㎲ (1,000 ns) revealed that these ligands could alter the native structure of the proteins and their flexibility. Our study suggests that suitable amiloride analogs might yield a prospective drug against coronavirus disease 2019.
Keywords
COVID-19; hexamethylene amiloride; SARS-CoV-2 E; virology; viroporin;
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