{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:12:40Z","timestamp":1767834760933,"version":"3.49.0"},"reference-count":129,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T00:00:00Z","timestamp":1682208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation (NRF)","doi-asserted-by":"publisher","award":["129778"],"award-info":[{"award-number":["129778"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation (NRF)","doi-asserted-by":"publisher","award":["21\/76"],"award-info":[{"award-number":["21\/76"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001323","name":"Poliomyelitis Research Foundation (PRF)","doi-asserted-by":"publisher","award":["129778"],"award-info":[{"award-number":["129778"]}],"id":[{"id":"10.13039\/501100001323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001323","name":"Poliomyelitis Research Foundation (PRF)","doi-asserted-by":"publisher","award":["21\/76"],"award-info":[{"award-number":["21\/76"]}],"id":[{"id":"10.13039\/501100001323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The emergence of drug-resistant Human Immunodeficiency Virus-1 strains against anti-HIV therapies in the clinical pipeline, and the persistence of HIV in cellular reservoirs remains a significant concern. Therefore, there is a continuous need to discover and develop new, safer, and effective drugs targeting novel sites to combat HIV-1. The fungal species are gaining increasing attention as alternative sources of anti-HIV compounds or immunomodulators that can escape the current barriers to cure. Despite the potential of the fungal kingdom as a source for diverse chemistries that can yield novel HIV therapies, there are few comprehensive reports on the progress made thus far in the search for fungal species with the capacity to produce anti-HIV compounds. This review provides insights into the recent research developments on natural products produced by fungal species, particularly fungal endophytes exhibiting immunomodulatory or anti-HIV activities. In this study, we first explore currently existing therapies for various HIV-1 target sites. Then we assess the various activity assays developed for gauging antiviral activity production from microbial sources since they are crucial in the early screening phases for discovering novel anti-HIV compounds. Finally, we explore fungal secondary metabolites compounds that have been characterized at the structural level and demonstrate their potential as inhibitors of various HIV-1 target sites.<\/jats:p>","DOI":"10.3390\/v15051039","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T01:35:44Z","timestamp":1682300144000},"page":"1039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Developments in Exploring Fungal Secondary Metabolites as Antiviral Compounds and Advances in HIV-1 Inhibitor Screening Assays"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-1308","authenticated-orcid":false,"given":"Bruce","family":"Nzimande","sequence":"first","affiliation":[{"name":"Discipline of Medical Microbiology, School of Laboratory Medicine and Medical Sciences, Medical School, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-3951","authenticated-orcid":false,"given":"John P.","family":"Makhwitine","sequence":"additional","affiliation":[{"name":"Discipline of Medical Microbiology, School of Laboratory Medicine and Medical Sciences, Medical School, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-9201","authenticated-orcid":false,"given":"Nompumelelo P.","family":"Mkhwanazi","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2323-282X","authenticated-orcid":false,"given":"Sizwe I.","family":"Ndlovu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Technology, Doornfontein Campus, University of Johannesburg, Johannesburg 2028, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,23]]},"reference":[{"key":"ref_1","unstructured":"(2023, April 13). 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