{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sharma K"],"funding":["King Saud University, Riyadh, Saudi Arabia","King Saud University"],"pagination":["1406"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10976223"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(6)"],"pubmed_abstract":["SARS-CoV, an RNA virus, is contagious and displays a remarkable degree of adaptability, resulting in intricate disease presentations marked by frequent genetic mutations that can ultimately give rise to drug resistance. Targeting its viral replication cycle could be a potential therapeutic option to counter its viral growth in the human body leading to the severe infectious stage. The M<sup>pro</sup> of SARS-CoV-2 is a promising target for therapeutic development as it is crucial for viral transcription and replication. The derivatives of β-diketone and coumarin have already been reported for their antiviral potential and, thus, are considered as a potential scaffold in the current study for the computational design of potential analogs for targeting the viral replication of SARS-CoV-2. In our study, we used novel diketone-hinged coumarin derivatives against the SARS-CoV-2 M<sup>Pro</sup> to develop a broad-spectrum antiviral agent targeting SARS-CoV-2. Through an analysis of pharmacokinetics and docking studies, we identified a list of the top 10 compounds that demonstrated effectiveness in inhibiting the SARS-CoV-2 MPro virus. On the basis of the pharmacokinetics and docking analyses, the top 5 novel coumarin analogs were synthesized and characterized. The thermodynamic stability of compounds <b>KS82</b> and <b>KS94</b> was confirmed by their molecular dynamics, and the stability of the simulated system indicated their inhibitory nature. Molecules <b>KS82</b> and <b>KS94</b> were further evaluated for their anti-viral potential using Vero E6 cells followed by RT-PCR assay against SARS-CoV-2. The test compound KS82 was the most active with the potential to inhibit SARS-CoV-2 replication in Vero E6 cells. These data indicate that KS82 prevents the attack of the virus and emerges as the primary candidate with promising antiviral properties."],"journal":["Molecules (Basel, Switzerland)"],"pubmed_title":["Design, Synthesis, and Biological Evaluation of Novel Coumarin Analogs Targeted against SARS-CoV-2."],"pmcid":["PMC10976223"],"funding_grant_id":["RSP2024R357"],"pubmed_authors":["Sharma P","Singh M","Mujwar S","Kapoor M","Mishra KK","Wani TA","Sharma K","Sharma SC"],"additional_accession":[]},"is_claimable":false,"name":"Design, Synthesis, and Biological Evaluation of Novel Coumarin Analogs Targeted against SARS-CoV-2.","description":"SARS-CoV, an RNA virus, is contagious and displays a remarkable degree of adaptability, resulting in intricate disease presentations marked by frequent genetic mutations that can ultimately give rise to drug resistance. Targeting its viral replication cycle could be a potential therapeutic option to counter its viral growth in the human body leading to the severe infectious stage. The M<sup>pro</sup> of SARS-CoV-2 is a promising target for therapeutic development as it is crucial for viral transcription and replication. The derivatives of β-diketone and coumarin have already been reported for their antiviral potential and, thus, are considered as a potential scaffold in the current study for the computational design of potential analogs for targeting the viral replication of SARS-CoV-2. In our study, we used novel diketone-hinged coumarin derivatives against the SARS-CoV-2 M<sup>Pro</sup> to develop a broad-spectrum antiviral agent targeting SARS-CoV-2. Through an analysis of pharmacokinetics and docking studies, we identified a list of the top 10 compounds that demonstrated effectiveness in inhibiting the SARS-CoV-2 MPro virus. On the basis of the pharmacokinetics and docking analyses, the top 5 novel coumarin analogs were synthesized and characterized. The thermodynamic stability of compounds <b>KS82</b> and <b>KS94</b> was confirmed by their molecular dynamics, and the stability of the simulated system indicated their inhibitory nature. Molecules <b>KS82</b> and <b>KS94</b> were further evaluated for their anti-viral potential using Vero E6 cells followed by RT-PCR assay against SARS-CoV-2. The test compound KS82 was the most active with the potential to inhibit SARS-CoV-2 replication in Vero E6 cells. These data indicate that KS82 prevents the attack of the virus and emerges as the primary candidate with promising antiviral properties.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-04T19:12:30.458Z","creation":"2025-04-04T19:12:30.458Z"},"accession":"S-EPMC10976223","cross_references":{"pubmed":["38543042"],"doi":["10.3390/molecules29061406"]}}