Antiviral Activities of Hibiscus sabdariffa L. Tea Extract Against Human Influenza A Virus Rely Largely on Acidic pH but Partially on a Low-pH-Independent Mechanism

Abstract

Influenza A virus (IAV) infection is perennially one of the leading causes of death worldwide. Effective therapy and vaccination are needed to control viral expansion. However, current anti-IAV drugs risk inducing drug-resistant virus emergence. Although intranasal administration of whole inactivated virus vaccine can induce efficient protective immunity, formalin and β-propiolactone are the currently used and harmful inactivating agents. Here, we analyzed the antiviral activity of hibiscus (Hibiscus sabdariffa L.) tea extract against human IAV and evaluated its potential as a novel anti-IAV drug and a safe inactivating agent for whole inactivated vaccine. The in vitro study revealed that the pH of hibiscus tea extract is acidic, and its rapid and potent antiviral activity relied largely on the acidic pH. Furthermore, the mouse study showed that the acidic extract was not effective for either therapeutic or vaccination purposes. However, hibiscus tea extract and protocatechuic acid, one of the major components of the extract, showed not only potent acid-dependent antiviral activity but also weak low-pHindependent activity. The low-pH-independent activity did not affect the conformation of immunodominant hemagglutinin protein. Although this low-pH-independent activity is very limited, it may be suitable for the application to medication and vaccination because this activity is not affected by the neutral blood environment and does not lose antigenicity of hemagglutinin. Further study of the low-pH-independent antiviral mechanism and attempts to enhance the antiviral activity may establish a novel anti-IAV therapy and vaccination strategy. Keywords Acidic pH • Anti-human influenza A viral activity • Antiviral drug therapy • Hibiscus tea extract • Natural substance • Whole inactivated vaccine

Saxifraga spinulosa-Derived Components Rapidly Inactivate Multiple Viruses Including SARS-CoV-2

“…Madin–Darby canine kidney (MDCK) cells were kindly provided by H. Nagano (Hokkaido Institute of Public Health, Sapporo, Japan). The composition of MDCK cell growth medium and IAV growth medium were as previously described [ 18 ]. FCV (F9 strain) and Crandell-Rees feline kidney (CRFK) cells were kindly provided by Dr. K. Maeda (Yamaguchi University, Yamaguchi, Japan).…”

Plant-Derived Food Grade Substances (PDFGS) Active Against Respiratory Viruses: A Systematic Review of Non-clinical Studies

“…Several PDFGS interfered with IAV entry into host cells ( Table 4 ). PDFGS such as edible bird nest (EBN) extracts, lectin-like compounds from Japanese plum, green tea, guava tea, isorhamnetin, tannins, HS, and polysaccharides from marine algae suppressed IAV-host cellular interactions through the inhibition of viral HA activities ( 41 , 45 , 51 , 57 , 66 , 67 ). PDFGS such as Portulaca oleracea (P. oleracea) extracts, quercetin and EBN are able to prevent virus-host interaction by binding with strong affinity to the surface coats of IAV ( 25 , 57 , 70 ).…”

“…HS, despite having an in vitro anti-IAV activity, in vivo studies showed that the aqueous extract of HS (8 mg), neither improved survival nor reduce virus titer in PR8 infected mice ( 45 ). Furthermore, the evidence they presented suggested that the observed in vitro anti-IAV activity of HS was due to the acidic nature of HS extract ( 45 ). In a separate experiment where they vaccinated mice with IAV inactivated by acidic HS, they observed an improvement in survival rate following subsequent IAV challenge.…”

“…In a separate experiment where they vaccinated mice with IAV inactivated by acidic HS, they observed an improvement in survival rate following subsequent IAV challenge. They however argued that the acidic nature of HS extract makes it unsuitable for vaccine development due to the possible alteration of IAV HA conformation and antigenic characteristics ( 45 ).…”

“…Potential biotransformation of the PDFGS under cellular conditions can affect the antiviral efficacy of PDFGS in human subjects. An instance is the recently reported association of the in vitro antiviral effects of HS extracts to their acidic properties ( 45 ). The buffering capacity of human cellular environment could potentially neutralize the HS acidity and so attenuate the observed in vitro antiviral effects of HS.…”