Venkatachalam Sankaran, Muralidharan Nisha, Pandian Ramesh, Sayed Yasien, Gromiha M Michael
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India.
Protein Structure-Function Research Laboratory, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2000, South Africa.
Viruses. 2025 Jun 16;17(6):850. doi: 10.3390/v17060850.
Acquired immunodeficiency syndrome (AIDS) is a chronic disease condition caused by the human immunodeficiency virus (HIV). The widespread availability of highly active antiretroviral therapies has helped to control HIV. There are ten FDA-approved protease inhibitors (PIs) that are used as part of antiretroviral therapies in HIV treatment. Importantly, all these drugs are designed and developed against the protease (PR) from HIV subtype B. On the other hand, HIV-1 PR subtype C, which is the most dominant strain in countries including South Africa and India, has shown resistance to PIs due to its genetic diversity and varied mutations. The emergence of resistance is concerning because the virus continues to replicate despite treatment; hence, it is necessary to develop drugs specifically against subtype C. This review focuses on the origin, genetic diversity, and mutations associated with HIV-1 PR subtype C. Furthermore, computational studies performed on HIV-1 PR subtype C and mutations associated with its resistance to PIs are highlighted. Moreover, potential research gaps and future directions in the study of HIV-1 PR subtype C are discussed.
获得性免疫缺陷综合征（艾滋病）是一种由人类免疫缺陷病毒（HIV）引起的慢性疾病。高效抗逆转录病毒疗法的广泛应用有助于控制HIV。有十种经美国食品药品监督管理局（FDA）批准的蛋白酶抑制剂（PIs）被用作HIV治疗中抗逆转录病毒疗法的一部分。重要的是，所有这些药物都是针对HIV B亚型的蛋白酶（PR）设计和开发的。另一方面，HIV-1 PR C亚型是包括南非和印度在内的国家中最主要的毒株，由于其基因多样性和多种突变，已显示出对PIs的耐药性。耐药性的出现令人担忧，因为尽管进行了治疗，病毒仍在继续复制；因此，有必要开发专门针对C亚型的药物。本综述重点关注与HIV-1 PR C亚型相关的起源、基因多样性和突变。此外，还强调了对HIV-1 PR C亚型及其对PIs耐药性相关突变进行的计算研究。此外，还讨论了HIV-1 PR C亚型研究中潜在的研究空白和未来方向。
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