{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:16:00Z","timestamp":1790806560155,"version":"4.1.0"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The continuing emergence of SARS-CoV-2 variants has highlighted the need to identify additional points for viral inhibition. Ribosome inactivating proteins (RIPs), such as MAP30 and Momordin which are derived from bitter melon (<jats:italic>Momordica charantia<\/jats:italic>), have been found to inhibit a broad range of viruses. MAP30 has been shown to potently inhibit HIV-1 with minimal cytotoxicity. Here we show that MAP30 and Momordin potently inhibit SARS-CoV-2 replication in A549 human lung cells (IC<jats:sub>50<\/jats:sub> ~ 0.2 \u03bcM) with little concomitant cytotoxicity (CC<jats:sub>50<\/jats:sub> ~ 2 \u03bcM). Both viral inhibition and cytotoxicity remain unaltered by appending a C-terminal Tat cell-penetration peptide to either protein. Mutation of tyrosine 70, a key residue in the active site of MAP30, to alanine completely abrogates both viral inhibition and cytotoxicity, indicating the involvement of its RNA N-glycosylase activity. Mutation of lysine 171 and lysine 215, residues corresponding to those in Ricin which when mutated prevented ribosome binding and inactivation, to alanine in MAP30 decreased cytotoxicity (CC<jats:sub>50<\/jats:sub> ~ 10 \u03bcM) but also the viral inhibition (IC<jats:sub>50<\/jats:sub> ~ 1 \u03bcM). Unlike with HIV-1, neither Dexamethasone nor Indomethacin exhibited synergy with MAP30 in the inhibition of SARS-CoV-2. From a structural comparison of the two proteins, one can explain their similar activities despite differences in both their active-sites and ribosome-binding regions. We also note points on the viral genome for potential inhibition by these proteins.<\/jats:p>","DOI":"10.1371\/journal.pone.0286370","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T18:12:35Z","timestamp":1688062355000},"page":"e0286370","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The ribosome-inactivating proteins MAP30 and Momordin inhibit SARS-CoV-2"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5089-635X","authenticated-orcid":true,"given":"Norman R.","family":"Watts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Eren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul 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