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The cell entry of SARS-CoV-2 depends on two host proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). There is currently no vaccine available and also no effective drug for the treatment of COVID-19. Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) as a novel gasotransmitter has been shown to protect against lung damage via its anti-inflammation, antioxidative stress, antiviral, prosurvival, and antiaging effects. In light of the research advances on H<jats:sub>2<\/jats:sub>S signaling in biology and medicine, this review proposed H<jats:sub>2<\/jats:sub>S as a potential defense against COVID-19. It is suggested that H<jats:sub>2<\/jats:sub>S may block SARS-CoV-2 entry into host cells by interfering with ACE2 and TMPRSS2, inhibit SARS-CoV-2 replication by attenuating virus assembly\/release, and protect SARS-CoV-2-induced lung damage by suppressing immune response and inflammation development. Preclinical studies and clinical trials with slow-releasing H<jats:sub>2<\/jats:sub>S donor(s) or the activators of endogenous H<jats:sub>2<\/jats:sub>S-generating enzymes should be considered as a preventative treatment or therapy for COVID-19. <\/jats:p>","DOI":"10.1152\/ajpcell.00187.2020","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T18:30:05Z","timestamp":1591727405000},"page":"C244-C249","source":"Crossref","is-referenced-by-count":53,"title":["H<sub>2<\/sub>S as a potential defense against COVID-19?"],"prefix":"10.1152","volume":"319","author":[{"given":"Guangdong","family":"Yang","sequence":"first","affiliation":[{"name":"Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada"},{"name":"Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, 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