The seafood Musculus senhousei shows anti-influenza A virus activity by targeting virion envelope lipids

Abstract

The seafood Musculus senhousei shows anti-influenza A virus activity by targeting virion envelope lipids, Biochemical Pharmacology (2020), doi: https://doi. AbstractMarine environments are known to be a new source of structurally diverse bioactive molecules. In this paper, we identified a porphyrin derivative of Pyropheophorbide a (PPa) from the mussel Musculus senhousei (M. senhousei) that showed broad anti-influenza A virus activity in vitro against a panel of influenza A viral strains. The analysis of the mechanism of action indicated that PPa functions in the early stage of virus infection by interacting with the lipid bilayer of the virion, resulting in an alteration of membrane-associated functions, thereby blocking the entry of enveloped viruses into host cells. In addition, the anti-influenza A virus activity of PPa was further assessed in mice infected with the influenza A virus. The survival rate and mean survival time of mice were apparently prolonged compared with the control group which was not treated with the drug. Therefore, PPa and its derivatives may represent lead compounds for controlling influenza A virus infection.Keywords: Marine food, Musculus senhousei, Pyropheophorbide a, Anti-influenza A virus activity, Enveloped virus. the H5N1 pseudo-typed virus screening approach, we identified the traditional Chinese seafood M. senhousei as showing a good inhibitory activity toward influenza A virus (IAV). The preliminary mechanistic study indicated that the antiviral activity of this food resulted from the inhibition of virus entry during early infection. We then investigated the bioactive components of this mussel using a bioassay-guided approach, from which a porphyrin derivative named pyropheophorbide a (PPa) that showed significant anti-IAV activity in vitro was isolated and identified, indicating a potential application of this molecule in the development of new antiviral agents.IAVs are enveloped viruses, and the viral envelopes are derived from portions of the host cell membranes and function to cover the capsids to protect the packaged viral genome 7 . In addition to the lipid bilayer, the viral envelope also contains viral glycoproteins, such as hemagglutinin (HA), neuraminidase (NA) and the viral M2 protein. These components, including lipid bilayers and associated proteins, play important roles in the process of viral infection 8,9 . As a result, they are viewed as promising tools for the development of new anti-influenza A drugs 10 .The HA glycoprotein consisting of two subunits, HA1 and HA2, is located on the surface of the envelope and is responsible for binding to receptor sites on the host membrane (HA1) and mediating the fusion between viral and host membranes (HA2).Following fusion, the viral genome is able to enter and subsequently infect the host cells 11 .The lipid bilayer is a major component of the IAV envelope. To date, a number of molecules targeting virion envelope lipids to interfere with the fusion of viral-host cellular membranes have been reported 12,13 . These molecul...

Broad-spectrum antivirals of protoporphyrins inhibit the entry of highly pathogenic emerging viruses

“…S1C). This conclusion is consistent with the results of our previous study, showing that the antiviral activity of Pyropheophorbide a (PPa) was due to the interaction with the viral membrane or biophysical interference with the virus-cell membrane fusion process, which resulted in blocking the entry of an enveloped virus into cells (17).…”

“…The biological activity test showed that PPa exhibited good antiviral activity against a panel of influenza A viruses. The mechanism of action study indicated that PPa exerted its inhibitory effect in the early stage of virus infection by interacting with the lipid bilayer function of the virion, blocking the entry of enveloped viruses into host cells (17).…”

A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses

“…However, pyroPba was also more toxic, and hence the final selectivity index was not higher than that of Pba. PyroPba has already been demonstrated to be active against IAV, RSV (respiratory syncytial virus), and SARS-CoV-2 ( 41 ) . The authors studied the mechanism of action of pyroPba against IAV and showed that the molecule targets the membrane of the virus and not the surface glycoproteins, a mechanism which is consistent with the one that we observed for Pba in our study.…”

“…The authors studied the mechanism of action of pyroPba against IAV and showed that the molecule targets the membrane of the virus and not the surface glycoproteins, a mechanism which is consistent with the one that we observed for Pba in our study. A requirement for photo-activation of pyroPba was not investigated nor mentioned by Chen et al ( 41 ) . Porphyrins have already been described for their antiviral activity ( 25 , 42 ) .…”

Pheophorbide a Derivatives Exert Antiwrinkle Effects on UVB-Induced Skin Aging in Human Fibroblasts

“…In addition, PA is reported to have antiwrinkle activity in UV-stimulated skin tissue through suppression of MMP-1 and MMP-3 expression (Granted patent: US 20170189292). Pyropheophorbide a (PyroPA), a decarboxylated derivative of PA, has been reported to inhibit the growth of hepatitis C virus [ 18 ] and influenza A [ 29 ]. PyroPA and pyropheophorbide a methyl ester (PyroPA-ME), based on its photosensitizing characteristics, can also be applied in anticancer PDT [ 30 , 31 ].…”