ABSTRACT
There is a daunting public health emergency due to the emergence and rapid global spread of the new omicron variants of SARS-CoV-2. The variants differ in many characteristics, such as transmissibility, antigenicity and the immune system of the human hosts' shifting responses. This change in characteristics raises concern, as it leads to unknown consequences and also raises doubts about the efficacy of the currently available vaccines. As of March 2022, there are five variants of SARS-CoV-2 disseminating: the alpha, the beta, the gamma, the delta and the omicron variant. The omicron variant has more than 30 mutations on the spike protein, which is used by the virus to enter the host cell and is also used as a target for the vaccines. In this work, we studied the possible anti-COVID-19 effect of two molecules by molecular docking using Autodock Vina and molecular dynamic simulations using Gromacs 2020 software. We docked amoxicillin and clavulanate to the main protease (Mpro), the RNA-dependent RNA polymerase (RdRp) and the spike protein receptor-binding domain (SRBD) of the wild type with the two variants (delta and omicron) of SARS-CoV-2. The docking results show that the ligands bound tightly with the SRBD of the omicron variant, while the dynamic simulation revealed the ability of amoxicillin to bind to the SRBD of both variants' delta and omicron. The high number of mutations that occurred in both variants increases the affinity of amoxicillin towards them. Communicated by Ramaswamy H. Sarma.
ABSTRACT
BACKGROUND: 2019-nCoVis, a novel coronavirus was isolated and identified in 2019 in the city of Wuhan, China. On February 17, 2020 and according to the World Health Organization, 71, 429 confirmed cases worldwide were identified, among them 2162 new cases were recorded in the last 24 hours. One month later, the confirmed cases jumped to 179111, with 11525 new cases in the last 24 hours, with 7426 total deaths. No drug or vaccine is present at the moment for human and animal coronavirus. METHODS: The inhibition of 3CL hydrolase enzyme provides a promising therapeutic principle for developing treatments against CoViD-19. The 3CLpro (Mpro) is known for involving in counteracting the host innate immune response. RESULTS: This work presents the inhibitory effect of some natural compounds against 3CL hydrolase enzyme, and explains the main interactions in inhibitor-enzyme complex. Molecular docking study was carried out using Autodock Vina. By screening several molecules, we identified three candidate agents that inhibit the main protease of coronavirus. Hispidin, lepidine E, and folic acid are bound tightly in the enzyme, therefore strong hydrogen bonds have been formed (1.69-1.80Å) with the active site residues. CONCLUSION: This study provides a possible therapeutic strategy for CoViD-19.