# Resveratrol: A Review on the Biological Activity and Applications
## 14 Antiviral Properties  
Several studies found that RSV has a cooperative effect in association with nucleoside analogs, such as zidovudine, zalcitabine, and didanosine, stimulating their activity against human immunodeficiency virus type 1 (HIV-1). Individual RSV did not produce cell toxicity and inhibited viral replication, while in peripheral blood mononuclear cells infected with human T-cell lymphotropic virus-IIIB (HTLV-IIIB) isolate of HIV, it decreased the inhibitory concentration of the nucleoside analogs. An identical antiviral effect was documented when didanosine was merged with RSV in peripheral blood mononuclear cells infected with HIV-1. The inclusion of RSV determined a 10-time amplification of the antiviral action of didanosine in infected monocyte-derived macrophages. In a test on HTLV-IIIB-infected T-lymphocytes, the RSV-didanosine mixture, but not independently, inhibited the viral infection [249].  
RSV has been demonstrated to have an anti-herpes simplex virus (HSV) effect in vitro. To examine its activity in vivo, the abraded skin of mice was infected with HSV-1, and RSV cream was applied locally. The following findings were made: 25% RSV cream successfully inhibited lesion progression, while 12.5% RSV cream had the same effect only if applied one hour after infection; neither one was effective if applied twelve hours after infection. In addition, RSV cream, 10% docosanol cream, and 5% acyclovir ointment were compared. RSV and acyclovir substantially obstructed the progression of HSV-1-caused epidermis lesions, while docosanol had no influence. The application of RSV provoked no dermal toxicity, such as erythema, scaling, crusting, lichenification, or excoriation [250].  
Regarding human cytomegalovirus replicating, extremely high concentrations of RSV were necessary to generate cytotoxicity as opposed to developing or stagnant human embryonic long fibroblasts. RSV obstructed the virus-activated epidermal growth factor receptor and PI3K signal transduction, as well as NF-\(\kappa\)B and Sp1 transcription factor activation, immediately post-infection. The mechanisms of the cytomegalovirus, such as DNA replication, PI3K signaling, and transcription factor activation, were all suppressed by RSV. However, the virucidal action was incompatible, and the antiviral effect of RSV was significantly reduced when administered four hours after infection. As a result, this phytocompound engaged amid attachment and entry via arrest of epidermal growth factor receptor activation and its succeeding effectors [251].  
Worldwide, rotavirus is the principal originator of viral gastroenteritis in children, with no efficient therapy. The anti-rotavirus impact of RSV was inspected in vitro, including the production of virion descendants, viral polyprotein expression, genomic RNA synthesis, antigen clearance, and alterations in proinflammatory cytokines/chemokines in infant mouse cells. The assays concluded that RSV strongly limited rotavirus replication by inhibiting RNA formation, protein expression, viroplasm plaque generation, progeny virion synthesis, and cytopathy. RSV treatment ameliorated the gravity of diarrhea, reduced viral titers, and alleviated correlated symptoms [252].  
The high-occurrence hepatitis B virus infection requires successful therapeutics. A recent study prospected the influence of RSV on hepatitis B virus replication, utilizing in vitro and in vivo analysis, and confirmed that it suppresses cytotoxicity and virus replication. Through its mechanism of action via reducing miR-155 expression and stimulating autophagy, RSV proved to be a promising novel approach for the treatment of hepatitis B virus infection [253].