Extracts of the medicinal herb Sanguisorba officinalis inhibit the entry of human immunodeficiency virus-1

Abstract

Highly active antiretroviral therapy (HAART) has been successful in reducing human immunodeficiency virus (HIV)-1-associated morbidity and mortality since its introduction in 1996. However, it fails to eradicate HIV-1 infection. The high cost of life-long highly active antiretroviral therapy and the emergence of drug resistance among HIV-1-infected individuals have brought renewed pressure for the discovery of novel antivirals and alternative medicines. Traditional Chinese medicine (TCM) is a complementary and alternative medicine, and serves as a rich resource for new drug development. Despite the almost 100 plant-derived compounds that are in clinical trials, few target HIV-1 infection. In this study, we discovered that Sanguisorba officinalis extract (SOE) has anti-HIV-1 properties. Using a cell-based assay and single-cycle luciferase reporter viruses pseudotyped with envelopes from HIV-1 or control viruses, we found that SOE exhibited significant inhibitory ability against both CCR5 and CXCR4 tropic HIV-1 (ADA and HXB2), with respective IC50 values of 1.91 ± 0.16 μg/mL and 3.70 ± 0.53 μg/mL. SOE also inhibited simian immunodeficiency virus infection but failed to block vesicular stomatitis virus, severe acute respiratory syndrome coronavirus, and influenza H5N1 pseudoviruses. Furthermore, we showed that SOE had no effect on postentry events of HIV-1 replication. Because SOE pretreatment with the virus but not with cell lines expressing viral receptors showed the maximal inhibitory activity, we can state that SOE probably blocks entry by acting on the viral envelope directly. In addition, SOE was able to inhibit reverse transcriptase inhibitor resistant viruses (K103N, Y188L, and K103N/Y188L/G190A) and a protease inhibitor resistant strain (PI-2840). Our findings demonstrate SOE as a novel and specific entry inhibitor, which sheds light on the discovery of anti-HIV-1 drugs from traditional herbal medicines.