The current emergency due to the worldwide spread of the COVID-19 caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness has not yet been assessed. The main protease (M^pro) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent M^pro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by a hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed this study to highlight some crucial aspects. Seventeen potential SARS-CoV-2 M^pro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

Viral infections are responsible for several chronic and acute diseases in both humans and animals. Despite the incredible progress in human medicine, several viral diseases, such as acquired immunodeficiency syndrome, respiratory syndromes, and hepatitis, are still associated with high morbidity and mortality rates in humans. Natural products from plants or other organisms are a rich source of structurally novel chemical compounds including antivirals. Indeed, in traditional medicine, many pathological conditions have been treated using plant-derived medicines. Thus, the identification of novel alternative antiviral agents is of critical importance. In this review, we summarize novel phytochemicals with antiviral activity against human viruses and their potential application in treating or preventing viral disease.

An earlier report has shown that herpes simplex virus 1 virions package RNA. Experiments designed to reveal the identity of the virion proteins capable of binding the RNA and to show whether the mRNA carried in the newly infected cells was expressed showed the following: ( i ) ³² P-labeled riboprobe generated by in vitro transcription of the U _S 8.5 ORF bound three proteins identified as the products of U _S 11, U _L 47, and U _L 49 (VP22) genes. ( ii ) Viral RNA was bound to U _L 47 or U _S 11 proteins immune precipitated from cells transduced with baculoviruses expressing U _L 47 or U _S 11 and then superinfected with HSV-1 under conditions that blocked DNA synthesis and assembly of virions. ( iii ) Virions were purified from cells transduced with a baculovirus encoding a U _S 8.5 protein fused to green fluorescent protein and superinfected with an HSV-1 mutant lacking the U _S 8–12 genes. HEp-2 cells infected with these virions expressed the chimeric protein in ≈1% of infected cells. ( iv ) In mixed cultures, untreated Vero cells acquired the mRNA encoding the green fluorescent–U _S 8.5 chimeric protein from HEp-2 cells doubly transduced with the genes encoding VP22 and the chimeric protein. The transfer was RNase sensitive and VP22 dependent, indicating that the RNA encoded by the chimeric gene was transferred to Vero cells as mRNA. We conclude that ( i ) three virion proteins are capable of binding RNA; ( ii ) the packaged RNA can be expressed in newly infected cells; and ( iii ) the U _L 47 protein was earlier reported to shuttle from nucleus to the cytoplasm and may transport RNA. VP22 thus appears to be a member of a new class of viral proteins whose major function is to bind and transport infected cell mRNA to uninfected cells to create the environment for effective initiation of infection.