Dataset Information

The main protease and RNA-dependent RNA polymerase are two prime targets for SARS-CoV-2.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented global health crisis. It is particularly urgent to develop clinically effective therapies to contain the pandemic. The main protease (M^pro) and the RNA-dependent RNA polymerase (RdRP), which are responsible for the viral polyprotein proteolytic process and viral genome replication and transcription, respectively, are two attractive drug targets for SARS-CoV-2. This review summarizes up-to-date progress in the structural and pharmacological aspects of those two key targets above. Different classes of inhibitors individually targeting M^pro and RdRP are discussed, which could promote drug development to treat SARS-CoV-2 infection.

SUBMITTER: Jin Z

PROVIDER: S-EPMC7680044 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The main protease and RNA-dependent RNA polymerase are two prime targets for SARS-CoV-2.

Jin Zhenming Z Wang Haofeng H Duan Yinkai Y Yang Haitao H

Biochemical and biophysical research communications 20201121

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented global health crisis. It is particularly urgent to develop clinically effective therapies to contain the pandemic. The main protease (M<sup>pro</sup>) and the RNA-dependent RNA polymerase (RdRP), which are responsible for the viral polyprotein proteolytic process and viral genome replication and transcription, respectively, are two attractive drug t ...[more]

PMID: 33288200

Similar Datasets

Project description:An outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been recognized as a global health concern. Since, no specific antiviral drug is proven effective for treatment against COVID-19, identification of new therapeutics is an urgent need. In this study, flavonoid compounds were analyzed for its inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. Virtual docking was performed for screening of flavonoid compounds retrieved from PubChem against the main protease of SARS-CoV-2 using COVID-19 docking server. The cut off of dock score was set to >-9 kcal/mol and screened compounds were individually docked against main protease, RNA-dependent RNA polymerase, and spike proteins using AutoDock 4.1 software. Finally, lead flavonoid compounds were subjected to ADMET analysis. A total of 458 flavonoid compounds were virtually screened against main protease target and 36 compounds were selected based on the interaction energy value >-9 kcal/mol. Furthermore, these compounds were individually docked against protein targets and top 10 lead compounds were identified. Among the lead compounds, agathisflavone showed highest binding energy value of -8.4 kcal/mol against main protease, Albireodelphin showed highest dock score of -9.8 kcal/mol and -11.2 kcal/mol against RdRp, and spike proteins, respectively. Based on the high dock score and ADMET properties, top 5 lead molecules such as Albireodelphin, Apigenin 7-(6″-malonylglucoside), Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside) and (-)-Maackiain-3-O-glucosyl-6″-O-malonate were identified as potent inhibitors against main protease, RdRp, and spike protein targets of SARS-CoV-2. These all compounds are having non-carcinogenic and non-mutagenic properties. This study finding suggests that the screened compounds include Albireodelphin, Apigenin 7-(6″-malonylglucoside), Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside) and (-)-Maackiain-3-O-glucosyl-6″-O-malonate could be the potent inhibitors of SARS-CoV-2 targets.

Project description:Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) being a causative agent for global pandemic disease nCOVID'19, has acquired much scientific attention for the development of effective vaccines and drugs. Several attempts have been made to explore repurposing existing drugs known for their anti-viral activities, and test the traditional herbal medicines known for their health benefiting and immune-boosting activity against SARS-CoV-2. In this study, efforts were made to examine the potential of 605 phytochemicals from 37 plant species (of which 14 plants were endemic to India) and 139 antiviral molecules (Pubchem and Drug bank) in inhibiting SARS-CoV-2 multiple protein targets through a virtual screening approach. Results of our experiments revealed that SARS-CoV-2 MPro shared significant disimilarities against SARS-CoV MPro and MERS-CoV MPro indicating the need for discovering novel drugs. This study has screened the phytochemical cyanin (Zingiber officinale) which may exhibit broad-spectrum inhibitory activity against main proteases of SARS-CoV-2, SARS-CoV and MERS-CoV with binding energies of (-) 8.3 kcal/mol (-) 8.2 kcal/mol and (-) 7.7 kcal/mol respectively. Amentoflavone, agathisflavone, catechin-7-o-gallate and chlorogenin were shown to exhibit multi-target inhibitory activity. Further, Mangifera indica, Anacardium occidentale, Vitex negundo, Solanum nigrum, Pedalium murex, Terminalia chebula, Azadirachta indica, Cissus quadrangularis, Clerodendrum serratum and Ocimum basilicumaree reported as potential sources of phytochemicals for combating nCOVID'19. More interestingly, this study has highlighted the anti-viral properties of the traditional herbal formulation "Kabasura kudineer" recommended by AYUSH, a unit of Government of India. Short listed phytochemicals could be used as leads for future drug design and development. Genomic analysis of identified herbal plants will help in unraveling molecular complexity of therapeutic and anti-viral properties which proffer lot of chance in the pharmaceutical field for researchers to scout new drugs in drug discovery.

Dataset Information

The main protease and RNA-dependent RNA polymerase are two prime targets for SARS-CoV-2.

Publications

The main protease and RNA-dependent RNA polymerase are two prime targets for SARS-CoV-2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets