Lectins as Promising Therapeutics for the Prevention and Treatment of HIV and Other Potential Coinfections

Mazalovska, Milena; Kouokam, J. Calvin

of HIV patients are coinfected with HCV [68] . Infection with HCV causes either acute or chronic infection, which can progress to cirrhosis with the need for liver transplantation [69] . Usually, HCV-HIV coinfection is associated with a faster [39] progression to cirrhosis and liver failure and shows poor response to treatment [70, 71] . As the most potent anti-HIV lectin described so far, GRFT has been widely assessed for its activities against other enveloped viruses. GRFT has been shown to mitigate HCV infection of mice harboring human primary hepatocytes in the liver and prevents in vitro HCV infection of Huh-7 hepatoma cells [54] . Notably, GRFT binds to the HCV envelope glycoproteins E1 and E2, blocking viral entry into human hepatocytes [72] . In addition to GRFT, other lectins, including those with anti-HIV activities, have the ability to bind and neutralize HCV. HCV is an enveloped virus, like HIV, with two heavily glycosylated glycoproteins that include E1 and E2 [73] . E1 contains 4-5 N-linked glycosylation sites and E2 up to 11, many of which are high-mannose-type glycans that ensure proper folding, attachment, and entry, protecting the virus from neutralizing antibodies [74] . Targeting viral entry with lectins could potentially be a new strategy to combat HCV. Indeed, cyanovirin-N can inhibit HCV infection by binding the N-linked glycans on its surface, preventing the interaction between E2 and the entry receptor CD81 [53] . Other studies demonstrated that CV-N, Microcystis viridis lectin (MVL), and Galanthus nivalis agglutinin (GNA) inhibit HCV in vitro, with IC50 values of 0.6 nM, 30.4 nM, and 11.1 nM, respectively, likely through distinct and complex modes of action [55, 75] .