Prevention and Treatment of SHIVAD8 Infection in Rhesus Macaques by a Potent D-peptide HIV Entry Inhibitor

Abstract

Cholesterol-PIE12-trimer (CPT31) is a potent D-peptide HIV entry inhibitor that targets the highly conserved gp41 N-peptide pocket region. CPT31 exhibited strong inhibitory breadth against diverse panels of primary virus isolates. In a SHIV macaque model, CPT31 prevented infection from a single high-dose rectal challenge. In chronically infected animals, CPT31 monotherapy rapidly reduced viral load by ~2 logs before rebound occurred due to the emergence of drug resistance. In chronically infected animals with viremia initially controlled by combination antiretroviral therapy (cART), CPT31 monotherapy prevented viral rebound after discontinuation of cART. These data establish CPT31 as a promising new candidate for HIV prevention and treatment.

Antivirals with common targets against highly pathogenic viruses

“…In 2018, albuvirtide was approved by the China Food and Drug Administration (CFDA) for weekly medication for HIV-infected patients. Very recently, Nishimura et al reported that a D-peptide, CPT31, targeting HIV HR1 prevented HIV infection, rapidly reduced viral load, and prevented viral rebound after discontinuation of canonical antiretroviral therapy for 3-month interval administration in macaques (Nishimura et al, 2020). Peptides from viral HR1 can also inhibit viral infection by binding HR2, but they are usually less potent than HR2-peptides.…”