Fostemsavir is the phosphonooxymethyl prodrug of temsavir, which is a HIV-1 attachment inhibitor that binds to the gp120 subunit within the HIV-1 gp160 envelope glycoprotein. Fostemavir is the first attachment inhibitor to receive FDA approval, granted in July 2020, for use in combination with other antretrovirals. The gp120 subunit within the gp160 envelpe glycoprotein of HIV-1 are responsible for facilitating attachment of the virus to the host cell CD4 receptors. Fostemsavir is metabolized in the microvilli of the small intestine into temsavir by the enzyme Intestinal-type alkaline phosphatase. It is transported into the blood where temsavir inhibits the envelope glycoprotein of HIV-1 by binding directly to the gp120 subunit, which inhibits the viral interaction with host CD4 receptors, thereby preventing the initial attachment of the virus. It has also been shown to inhibit other gp120-dependent post-attachment steps required for viral entry. The inability for the virus to attach and release viral components into the host cell greatly reduces the replication of the virus.

Fostemsavir Pathway References