{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:52:52Z","timestamp":1787169172532,"version":"build-2736575974"},"reference-count":124,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2320-B-037-035-MY3"],"award-info":[{"award-number":["MOST 108-2320-B-037-035-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to display particular patterns of genetic diversity in the genome across geographical regions. These variations in the virus and genetic variation in human populations can determine virus transmissibility and coronavirus disease 2019 (COVID-19) severity. Genetic variations and immune differences in human populations could be the driving forces in viral evolution. Recently emerged SARS-CoV-2 variants show several mutations at the receptor binding domain in the spike (S) glycoprotein and contribute to immune escape and enhanced binding with angiotensin 1-converting enzyme 2 (ACE2). Since ACE2 and transmembrane protease serine 2 (TMPRSS2) play important roles in SARS-CoV-2 entry into the cell, genetic variation in these host entry-related proteins may be a driving force for positive selection in the SARS-CoV-2 S glycoprotein. Dendritic or liver\/lymph cell-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin is also known to play vital roles in several pathogens. Genetic variations of these host proteins may affect the susceptibility to SARS-CoV-2. This review summarizes the latest research to describe the impacts of genetic variation in the viral S glycoprotein and critical host proteins and aims to provide better insights for understanding transmission and pathogenesis and more broadly for developing vaccine\/antiviral drugs and precision medicine strategies, especially for high risk populations with genetic risk variants.<\/jats:p>","DOI":"10.3390\/ijms22063060","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T11:48:22Z","timestamp":1615981702000},"page":"3060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["SARS-CoV-2 Entry Related Viral and Host Genetic Variations: Implications on COVID-19 Severity, Immune Escape, and Infectivity"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3813-7737","authenticated-orcid":false,"given":"Szu-Wei","family":"Huang","sequence":"first","affiliation":[{"name":"Model Development Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4183-3872","authenticated-orcid":false,"given":"Sheng-Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Clinical Microbiology Laboratory, Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). 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