Lectins: a potential gap in the HIV-1 drugs puzzle

Together with most recent Coronavirus-related diseases, the global human immunodeficiency virus (HIV) epidemic is one of the worst public-health crisis of our time. Even if in recent years our understanding of the HIV viral physiopathology has significantly improved as well as the infection treatment, there is an urgent need of new antiviral agents due to rising drug resistance, treatment-associated toxicity and poor bioavailability. For centuries natural products have been playing a major role in medicine and lectins are part of this partly unexplored world. Lectins are carbohydrate-binding proteins capable of inhibiting viral activities and may help to resolve current problematics regarding HIV-1 treatments with relatively low costs. Most of the studies conducted to date are focused on mannose binding lectins (MBLs) such as Griffithsin, Cyanovirin-N, BanLec. The majority of these lectins showed great abilities in neutralizing HIV-1, but with mitogenic activity on CD4+ T lymphocytes as a collateral effect. One of the few MBLs with no mitogenic activity is Griffithsin which is currently the most investigated molecule of this family and also the object of some clinical trials. My thesis reviewed two different approaches used to inhibit HIV-1 infection based on the lectins' ability to bind glycans. One approach was based on the crosslink between Griffithsin and glycans adorning the viral envelope surface; the other approach was based on interactions between a soybean lectin and glycosylated moieties on mammalian cells, in particular macrophages. Since the results are really hopeful, lectins may be introduced as anti-HIV-1 therapeutics in clinics not just based on the potential benefits for patients but also on their profitability for pharmaceutical companies. To this end, this thesis also reviews a Griffithsin low-cost synthesis method reproducible on a large-scale in a transplastomic plant system.