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Journal of Biological Chemistry ; 299(3 Supplement):S687, 2023.
Article in English | EMBASE | ID: covidwho-2318717
Topics in Antiviral Medicine ; 31(2):94, 2023.
Article in English | EMBASE | ID: covidwho-2317540
International Journal of Pharmaceutical Sciences and Research ; 14(3):1422-1434, 2023.
Article in English | EMBASE | ID: covidwho-2303729
Natural Product Communications ; 17(6), 2022.
Article in English | EMBASE | ID: covidwho-2299153
Iranian Journal of Medical Sciences ; 48(1 Supplement):123, 2023.
Article in English | EMBASE | ID: covidwho-2283288
Genes (Basel) ; 14(3)2023 02 28.
Article in English | MEDLINE | ID: covidwho-2258102


COVID-19 associated coagulopathy (CAC), characterized by endothelial dysfunction and hypercoagulability, evokes pulmonary immunothrombosis in advanced COVID-19 cases. Elevated von Willebrand factor (vWF) levels and reduced activities of the ADAMTS13 protease are common in CAC. Here, we aimed to determine whether common genetic variants of these proteins might be associated with COVID-19 severity and hemostatic parameters. A set of single nucleotide polymorphisms (SNPs) in the vWF (rs216311, rs216321, rs1063856, rs1800378, rs1800383) and ADAMTS13 genes (rs2301612, rs28729234, rs34024143) were genotyped in 72 COVID-19 patients. Cross-sectional cohort analysis revealed no association of any polymorphism with disease severity. On the other hand, analysis of variance (ANOVA) uncovered associations with the following clinical parameters: (1) the rs216311 T allele with enhanced INR (international normalized ratio); (2) the rs1800383 C allele with elevated fibrinogen levels; and (3) the rs1063856 C allele with increased red blood cell count, hemoglobin, and creatinine levels. No association could be observed between the phenotypic data and the polymorphisms in the ADAMTS13 gene. Importantly, in silico protein conformational analysis predicted that these missense variants would display global conformational alterations, which might affect the stability and plasma levels of vWF. Our results imply that missense vWF variants might modulate the thrombotic risk in COVID-19.

Blood Coagulation Disorders , COVID-19 , von Willebrand Factor , Humans , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/genetics , COVID-19/complications , COVID-19/genetics , Cross-Sectional Studies , Mutation, Missense , Polymorphism, Single Nucleotide , von Willebrand Factor/genetics
International Journal of Pharmaceutical Research and Allied Sciences ; 12(1), 2023.
Article in English | EMBASE | ID: covidwho-2240242
2022 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2022 ; : 2595-2602, 2022.
Article in English | Scopus | ID: covidwho-2223065
Journal of Clinical and Diagnostic Research ; 17(Supplement 1):64, 2023.
Article in English | EMBASE | ID: covidwho-2226190
Topics in Antiviral Medicine ; 30(1 SUPPL):63, 2022.
Article in English | EMBASE | ID: covidwho-1881039
Topics in Antiviral Medicine ; 30(1 SUPPL):88-89, 2022.
Article in English | EMBASE | ID: covidwho-1881034
Topics in Antiviral Medicine ; 30(1 SUPPL):182, 2022.
Article in English | EMBASE | ID: covidwho-1880819
Chinese Pharmacological Bulletin ; 36(11):1497-1501, 2020.
Article in Chinese | EMBASE | ID: covidwho-1863007
Int J Mol Sci ; 23(10)2022 May 18.
Article in English | MEDLINE | ID: covidwho-1862812


Animal coronaviruses (CoVs) have been identified to be the origin of Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and probably SARS-CoV-2 that cause severe to fatal diseases in humans. Variations of zoonotic coronaviruses pose potential threats to global human beings. To overcome this problem, we focused on the main protease (Mpro), which is an evolutionary conserved viral protein among different coronaviruses. The broad-spectrum anti-coronaviral drug, GC376, was repurposed to target canine coronavirus (CCoV), which causes gastrointestinal infections in dogs. We found that GC376 can efficiently block the protease activity of CCoV Mpro and can thermodynamically stabilize its folding. The structure of CCoV Mpro in complex with GC376 was subsequently determined at 2.75 Å. GC376 reacts with the catalytic residue C144 of CCoV Mpro and forms an (R)- or (S)-configuration of hemithioacetal. A structural comparison of CCoV Mpro and other animal CoV Mpros with SARS-CoV-2 Mpro revealed three important structural determinants in a substrate-binding pocket that dictate entry and release of substrates. As compared with the conserved A141 of the S1 site and P188 of the S4 site in animal coronaviral Mpros, SARS-CoV-2 Mpro contains N142 and Q189 at equivalent positions which are considered to be more catalytically compatible. Furthermore, the conserved loop with residues 46-49 in animal coronaviral Mpros has been replaced by a stable α-helix in SARS-CoV-2 Mpro. In addition, the species-specific dimerization interface also influences the catalytic efficiency of CoV Mpros. Conclusively, the structural information of this study provides mechanistic insights into the ligand binding and dimerization of CoV Mpros among different species.

COVID-19 , Peptide Hydrolases , Animals , Coronavirus 3C Proteases , Dimerization , Dogs , Endopeptidases , Ligands , Peptide Hydrolases/chemistry , SARS-CoV-2
Indian Journal of Clinical Biochemistry ; 36(SUPPL 1):S50, 2021.
Article in English | EMBASE | ID: covidwho-1767689
Indian Journal of Clinical Biochemistry ; 36(SUPPL 1):S12, 2021.
Article in English | EMBASE | ID: covidwho-1767670