INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION BY NONIMMUNOSUPPRESSIVE ANALOGS OF CYCLOSPORINE-A

Analogs of the immunosuppressive cyclic undecapeptide cyclosporin A (C sA) with substitutions in positions 1, 4, 6, and/or 11 were rationally designed to possess substantially diminished or no immunosuppressive activity, When these compounds were assayed for their capacity to inte rfere with the replication of human immunodeficiency virus, some displ ayed a potent antiviral activity in newly infected cells, However, onl y CsA could interfere with virus replication in persistently infected cells, One CsA analog with antiviral activity costimulated the phytohe magglutinin-induced production of interleukin 2 by human lymphocytes. Human immunodeficiency virus particles from drug-exposed cells showed lower infectivity than virions from untreated cells, Thus, these nonim munosuppressive analogs of CsA constitute a promising class of lead co mpounds to develop drugs for effective treatment of the acquired immun odeficiency syndrome.