Jadaun Pratiksha, Seniya Chandrabhan, Pal Sudhir Kumar, Kumar Sanjit, Kumar Pramod, Nema Vijay, Kulkarni Smita S, Mukherjee Anupam
ICMR-National AIDS Research Institute, Pune 411026, MH, India.
Meerut Institute of Engineering & Technology, Meerut 250005, UP, India.
Antioxidants (Basel). 2022 Sep 28;11(10):1942. doi: 10.3390/antiox11101942.
Antiretroviral therapy is the single existing therapy for patients infected with HIV; however, it has drawbacks in terms of toxicity and resistance. Thus, there is a continuous need to explore safe and efficacious anti-retroviral agents. C-Phycocyanin (C-PC) is a phycobiliprotein, which has been known for various biological properties; however, its effect on HIV-1 replication needs revelation. This study aimed to identify the inhibitory effects of C-PC on HIV-1 using and approaches and to assess its role in the generation of mitochondrial reactive oxygen species (ROS) during HIV-1 infection. anti-HIV-1 activity of C-PC was assessed on TZM-bl cells through luciferase gene assay against four different clades of HIV-1 strains in a dose-dependent manner. Results were confirmed in PBMCs, using the HIV-1 p24 antigen assay. Strong associations between C-PC and HIV-1 proteins were observed through molecular simulation-based interactions, and the mechanistic study confirmed its target by inhibition of reverse transcriptase and protease enzymes. Additionally, the generation of mitochondrial ROS was detected by the MitoSOX and DCF-DA probe through confocal microscopy. Furthermore, our results confirmed that C-PC treatment notably subdued the fluorescence in the presence of the virus, thus reduction of ROS and the activation of caspase-3/7 in HIV-1-infected cells. Overall, our study suggests C-PC as a potent and broad antiviral and antioxidant agent against HIV-1 infection.
抗逆转录病毒疗法是目前针对感染HIV患者的唯一现有疗法;然而,它在毒性和耐药性方面存在缺陷。因此,持续需要探索安全有效的抗逆转录病毒药物。C-藻蓝蛋白(C-PC)是一种藻胆蛋白,其具有多种生物学特性已为人所知;然而,其对HIV-1复制的影响尚待揭示。本研究旨在使用[具体方法1]和[具体方法2]方法确定C-PC对HIV-1的抑制作用,并评估其在HIV-1感染期间线粒体活性氧(ROS)产生中的作用。通过针对四种不同HIV-1毒株分支的荧光素酶基因测定,以剂量依赖方式在TZM-bl细胞上评估C-PC的抗HIV-1活性。使用HIV-1 p24抗原测定在PBMCs中证实了结果。通过基于分子模拟的相互作用观察到C-PC与HIV-1蛋白之间的强关联,并且[具体机制研究方法]机制研究通过抑制逆转录酶和蛋白酶来确认其靶点。此外,通过共聚焦显微镜使用MitoSOX和DCF-DA探针检测线粒体ROS的产生。此外,我们的结果证实,在存在病毒的情况下,C-PC处理显著降低了荧光,从而减少了HIV-1感染细胞中的ROS并激活了caspase-3/7。总体而言,我们的研究表明C-PC是一种针对HIV-1感染的强效且广谱的抗病毒和抗氧化剂。