{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:26:35Z","timestamp":1793661995347,"version":"4.5.1"},"reference-count":117,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Since the onset of the COVID-19 pandemic, remarkable progress has been made in the development of antiviral therapies for SARS-CoV-2. Several direct-acting antivirals, such as remdesivir, molnupiravir, and nirmatrelvir\/ritonavir, offer clinical benefits. These agents have significantly contributed to reducing the viral loads and duration of the illness, as well as the disease\u2019s severity and mortality. However, despite these advances, important limitations remain. The continued emergence of resistant SARS-CoV-2 variants highlights the urgent need for adaptable and durable therapeutic strategies. Therefore, this review aims to provide an updated overview of the main antiviral strategies that are used and the discovery of new drugs against SARS-CoV-2, as well as the therapeutic limitations that have shaped clinical management in recent years. The major challenges include resistance associated with viral mutations, limited treatment windows, and unequal access to treatment. Moreover, there is an ongoing need to identify novel compounds with broad-spectrum activity, improved pharmacokinetics, and suitable safety profiles. Combination treatment regimens represent a promising strategy to increase the efficacy of treating COVID-19 while minimizing the potential for resistance. Ideally, these interventions should be safe, affordable, and easy to administer, which would ensure broad global access and equitable treatment and enable control of COVID-19 cases and preparedness for future threats.<\/jats:p>","DOI":"10.3390\/v17081064","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:00:41Z","timestamp":1753884041000},"page":"1064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["SARS-CoV-2 Infection and Antiviral Strategies: Advances and Limitations"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0552-5995","authenticated-orcid":false,"given":"Vinicius Cardoso","family":"Soares","sequence":"first","affiliation":[{"name":"Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-361, Brazil"},{"name":"Center for Research, Innovation and Surveillance in COVID-19 and Health Emergencies, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-361, Brazil"},{"name":"Program of Immunology and Inflammation, Federal University of Rio de Janeiro UFRJ, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6702-706X","authenticated-orcid":false,"given":"Isabela Batista Gon\u00e7alves","family":"Moreira","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-361, Brazil"},{"name":"Center for Research, Innovation and Surveillance in COVID-19 and Health Emergencies, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-361, Brazil"},{"name":"Program of Immunology and Inflammation, Federal University of Rio de Janeiro UFRJ, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3104-0983","authenticated-orcid":false,"given":"Suelen Silva Gomes","family":"Dias","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-361, Brazil"},{"name":"Center for Research, Innovation and Surveillance in COVID-19 and Health Emergencies, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-361, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/s41564-022-01143-7","article-title":"SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway","volume":"7","author":"Willett","year":"2022","journal-title":"Nat. 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