SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: anin silicoperspective

Abstract

New treatment against SARS-CoV-2 now is a must. Nowadays, the world encounters a huge health crisis by the COVID-19 viral infection. Nucleotide inhibitors gave a lot of promising results in terms of its efficacy against different viral infections. In this work, molecular modeling, docking, and dynamics simulations are used to build a model for the viral protein RNA-dependent RNA polymerase (RdRp) and test its binding affinity to some clinically approved drugs and drug candidates. Molecular dynamics is used to equilibrate the system upon binding calculations to ensure the successful reproduction of previous results, to include the dynamics of the RdRp, and to understand how it affects the binding. The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp. Additionally, Setrobuvir, YAK, and IDX-184, show better results, while four novel IDX-184 derivatives show promising results in attaching to the SARS-CoV-2 RdRp. There is an urgent need to specify drugs that can selectively bind and subsequently inhibit SARS-CoV-2 proteins. The availability of a punch of FDA-approved anti-viral drugs can help us in this mission, aiming to reduce the danger of COVID-19. The compounds 2 and 3 may tightly bind to the SARS-CoV-2 RdRp and so may be successful in the treatment of COVID-19.

Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach

“…Thus, there is an unmet requirement for the specific anti-COVID-19 therapeutics to limit the severity of the deadly disease. Various clinicians and researchers are engaged in investigating and developing antivirals using different strategies combining experimental and in-silico approaches (Elfiky, 2020;Enayatkhani et al, 2020;Enmozhi et al, 2020;Islam et al, 2020;Jin et al, 2020;Khan, Jha, et al, 2020;Khan, Zia, et al, 2020;Qamar et al, 2020;Sinha et al, 2020) with the goal of identifying novel, selective and potent therapeutic agents.…”

Remdesivir in the treatment of coronavirus disease 2019 (COVID-19): a simplified summary

“…The CoV family has a sizable homogeneous "spike protein" (Figure 1). The role of the spike (S) protein, which is composed of 1300 amino acids (Elfiky, 2020b), is to interact with the host cells, such as the pulmonary and parabronchial epithelial cell, and assists the coronavirus to enter through the epithelial cell membrane (Boopathi et al, 2020;Xia et al, 2020).…”

Using X-ray images and deep learning for automated detection of coronavirus disease

“…It is therefore considered that close contact with a sick person is necessary to transmit the disease: the same place of residence, direct contact within one meter when talking, coughing, sneezing, or in the absence of protective measures. One of the other preferred vectors of virus transmission is in contact with unwashed hands soiled with droplets (Anwarul et al, 2020;Elfiky, 2020a;Enmozhi et al, 2020;Landry et al, 2020;Li, Guan, et al, 2020;Liu, Han, et al, 2020;Lu et al, 2020;Rowan & Laffey, 2020;Yang et al, 2020).…”