{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:01:57Z","timestamp":1789585317026,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Comput Chem"],"published-print":{"date-parts":[[2022,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The emergence of pandemic situations originated from severe acute respiratory syndrome (SARS)\u2010CoV\u20102 and its new variants created worldwide medical emergencies. Due to the non\u2010availability of efficient drugs and vaccines at these emergency hours, repurposing existing drugs can effectively treat patients critically infected by SARS\u2010CoV\u20102. Finding a suitable repurposing drug with inhibitory efficacy to a host\u2010protein is challenging. A detailed mechanistic understanding of the kinetics, (dis)association pathways, key protein residues facilitating the entry\u2013exit of the drugs with targets are fundamental in selecting these repurposed drugs. Keeping this target as the goal of the paper, the potential repurposing drugs, Nafamostat, Camostat, Silmitasertib, Valproic acid, and Zotatifin with host\u2010proteins HDAC2, CSK22, eIF4E2 are studied to elucidate energetics, kinetics, and dissociation pathways. From an ensemble of independent simulations, we observed the presence of single or multiple dissociation pathways with varying host\u2010proteins\u2010drug systems and quantitatively estimated the probability of unbinding through these specific pathways. We also explored the crucial gateway residues facilitating these dissociation mechanisms. Interestingly, the residues we obtained for HDAC2 and CSK22 are also involved in the catalytic activity. Our results demonstrate how these potential drugs interact with the host machinery and the specific target residues, showing involvement in the mechanism. Most of these drugs are in the preclinical phase, and some are already being used to treat severe COVID\u201019 patients. Hence, the mechanistic insight presented in this study is envisaged to support further findings of clinical studies and eventually develop efficient inhibitors to treat SARS\u2010CoV\u20102.<\/jats:p>","DOI":"10.1002\/jcc.26888","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T08:06:02Z","timestamp":1652169962000},"page":"1237-1250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mechanistic insights of key host proteins and potential repurposed inhibitors regulating SARS\n                    <scp>\u2010CoV<\/scp>\n                    \u20102 pathway"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3432-4498","authenticated-orcid":false,"given":"Debabrata","family":"Pramanik","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering Indian Institute of Technology Kanpur  Kanpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiswarya B.","family":"Pawar","sequence":"additional","affiliation":[{"name":"Prescience Insilico Private Limited  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudip","family":"Roy","sequence":"additional","affiliation":[{"name":"Prescience Insilico Private Limited  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8056-2115","authenticated-orcid":false,"given":"Jayant Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Indian Institute of Technology Kanpur  Kanpur India"},{"name":"Prescience Insilico Private Limited  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12040445"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.105948"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0234765"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2004.06.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijp.IJP_338_20"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2020.03.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2004.10.001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01472-06"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2021.661230"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/2210298101666210922143141"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.737007"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.8b03415"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.0c00175"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.06.040"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9RA02985K"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02019-20"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.034"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.130094"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-03078-z"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-020-03475-8"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-021-02708-7"},{"key":"e_1_2_7_23_1","first-page":"1","volume":"16","author":"Anand N. 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