Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti‐HIV microbicide

Abstract

Background The predominant mode of HIV‐1 transmission is by heterosexual contact. The cervical/vaginal mucosa is the main port of HIV entry in women. A safe and effective topical microbicide against HIV is urgently needed to prevent sexual transmission. Hence, we evaluated griffithsin (GRFT), a 12.7 kDa carbohydrate‐binding protein, both native and recombinant GRFT, potently inhibited both CXCR4‐and CCR5‐tropic HIV infection and transmission in vitro. Methods The antiviral efficacy of native and recombinant GRFT against CXCR4‐and CCR5‐tropic HIV and SHIV strains and SIVmac251 was evaluated by in vitro assays. We also evaluated the time course of antiviral activity and stability of GRFT in cervical/vaginal lavage as a function of pH 4–8. Results Griffithsin blocked CXCR4‐and CCR5‐tropic viruses at less than 1 nm concentrations and exhibited a high potency. GRFT was stable in cervical/vaginal lavage fluid and maintained a similar potency of anti‐HIV activity. GRFT is not only a highly potent HIV entry inhibitor, but also prevents cell fusion and cell‐to‐cell transmission of HIV. Conclusions The in vitro efficacy of GRFT revealed low cytotoxicity, high potency, rapid onset of antiviral activity and long‐term stability in cervical/vaginal lavage. GRFT is an excellent candidate for anti‐HIV microbicide development.

RT-SHIV, an infectious CCR5-tropic chimeric virus suitable for evaluating HIV reverse transcriptase inhibitors in macaque models

“…Virus replication was monitored by measuring either SIV p27 or HIV-1 p24 antigen in the culture supernatants by ELISA. This procedure was used to determine the 50% effective concentration (EC 50 ) for each drug [44]. …”

“…Cytotoxicity was evaluated by the standard MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay as described previously [45]. This assay was used to determine the 50% cytotoxic concentration (CC 50 ) for each drug [44]. All experiments were run in duplicate.…”

Biological Applications of Plants and Algae Lectins: An Overview

“…called griffithsin (GRFT) is a small mannose specific lectin that binds carbohydrates on HIV envelope glycoproteins and block HIV entry into target cells. GRFT is a candidate for development of anti-HIV microbicides [118,119]. GRFT was also able to inhibit the action of the pathogenic agent responsible for respiratory syndrome (SARS), the SARS coronavirus (SARS-CoV) [120].…”

Antiviral drug discovery: broad-spectrum drugs from nature

“…Interestingly, unlike other lectins, GRFT does not induce production of pro-inflammatory cytokines in treated human peripheral blood mononuclear cells 278 . It has been shown to safely protect mice from genital HSV 279 and monkeys from vaginal SIV infection 245 , thus having promising properties for preventing virus infections. Selection of GRFTresistant HIV variants has been observed.…”