Your browser doesn't support javascript.
Computational insights into tetracyclines as inhibitors against SARS-CoV-2 Mpro via combinatorial molecular simulation calculations.
Bharadwaj, Shiv; Lee, Kyung Eun; Dwivedi, Vivek Dhar; Kang, Sang Gu.
  • Bharadwaj S; Department of Biotechnology, Institute of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
  • Lee KE; Department of Biotechnology, Institute of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
  • Dwivedi VD; Centre for Bioinformatics, Computational and Systems Biology, Pathfinder Research and Training Foundation, Greater Noida, India. Electronic address: vivek_bioinformatics@yahoo.com.
  • Kang SG; Department of Biotechnology, Institute of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: kangsg@ynu.ac.kr.
Life Sci ; 257: 118080, 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-1152544
Semantic information from SemMedBD (by NLM)
1. Antibiotics compared_with Inhibitor
Subject
Antibiotics
Predicate
compared_with
Object
Inhibitor
2. Antibiotics compared_with Inhibitor
Subject
Antibiotics
Predicate
compared_with
Object
Inhibitor
ABSTRACT
The COVID-19 pandemic raised by SARS-CoV-2 is a public health emergency. However, lack of antiviral drugs and vaccine against human coronaviruses demands a concerted approach to challenge the SARS-CoV-2 infection. Under limited resource and urgency, combinatorial computational approaches to identify the potential inhibitor from known drugs could be applied against risen COVID-19 pandemic. Thereof, this study attempted to purpose the potent inhibitors from the approved drug pool against SARS-CoV-2 main protease (Mpro). To circumvent the issue of lead compound from available drugs as antivirals, antibiotics with broad spectrum of viral activity, i.e. doxycycline, tetracycline, demeclocycline, and minocycline were chosen for molecular simulation analysis against native ligand N3 inhibitor in SARS-CoV-2 Mpro crystal structure. Molecular docking simulation predicted the docking score >-7 kcal/mol with significant intermolecular interaction at the catalytic dyad (His41 and Cys145) and other essential substrate binding residues of SARS-CoV-2 Mpro. The best ligand conformations were further studied for complex stability and intermolecular interaction profiling with respect to time under 100 ns classical molecular dynamics simulation, established the significant stability and interactions of selected antibiotics by comparison to N3 inhibitor. Based on combinatorial molecular simulation analysis, doxycycline and minocycline were selected as potent inhibitor against SARS-CoV-2 Mpro which can used in combinational therapy against SARS-CoV-2 infection.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Tetracyclines / Betacoronavirus Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Life Sci Year: 2020 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Tetracyclines / Betacoronavirus Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Life Sci Year: 2020 Document Type: Article