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In this study, a small peptide fragment derived from major histocompatibility complex class I (MHC class I), designated MH-1, was investigated for its ability to interfere with the early stages of SARS-CoV-2 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Molecular docking was used to characterize the interaction between MH-1 and the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. The inhibitory effect of MH-1 on S protein\u2013ACE2 binding was further evaluated using an ACE2-functionalized electrochemical impedance spectroscopy (EIS) biosensing platform. Antiviral efficacy was assessed using SARS-CoV-2\u00a0S-pseudotyped lentiviruses and SARS-CoV-2 variants in different human cells. In vivo inhibitory efficacy of MH-1 was assessed in the K18-hACE2 mouse model, followed by lung viral load measurement and histopathological assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MH-1 peptide interacted with the S-RBD and disrupted S protein-ACE2 binding. MH-1 effectively reduced SARS-CoV-2 infection in cells that expressed different levels of ACE2 and TMPRSS2. Furthermore, MH-1 decreased the infection of SARS-CoV-2 in T lymphocytes that highly express HLA-C but have low levels of ACE2 and TMPRSS2. In animal studies, MH-1 reduced the viral load in the lungs of K18-hACE2 mice and reduced the infiltration of immune cells, including macrophages and T cells, into the lungs. Levels of lung damage and inflammatory cytokines were also reduced by MH-1 and restored to normal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings identify MH-1 as a promising prophylactic or early-stage intervention that inhibits SARS-CoV-2 infection by interfering with spike-mediated infection of pulmonary and immune cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-026-01434-3","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T06:54:50Z","timestamp":1771224890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HLA-C\u2013derived peptide MH-1 as an early-stage intervention against SARS-CoV-2 infection"],"prefix":"10.1186","volume":"32","author":[{"given":"Ting-Yan","family":"Jian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Yu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yu","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Heng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lik Voon","family":"Kiew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ling","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh-Te","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Chin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Chen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Xuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Syun","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sook Fan","family":"Yap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Chen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chuan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-An","family":"Kung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Nien","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Guei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ching","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Ru","family":"Shih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"issue":"57","key":"1434_CR1","doi-asserted-by":"publisher","first-page":"eabg6461","DOI":"10.1126\/sciimmunol.abg6461","volume":"6","author":"B Agerer","year":"2021","unstructured":"Agerer B, Koblischke M, Gudipati V, Monta\u00f1o-Gutierrez LF, Smyth M, Popa A, et al. 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