Screening of Influenza a (H1N1) Neuraminidase Inhibitor for Kabasura Kudineer, Nilavembu Kudineer and the Novel Formulation JACOM

<p>Due to erratic climate change, vector-borne diseases started flaring up from the second half of the last decade. Siddha medicine has been used as a public health tool to effectively manage chikungunya and dengue in the epidemics that happened in 2008 and 2016. Tamil Nadu government has made enormous efforts to control vector-borne diseases. Due to which morbidity and mortality due to vector borne diseases came down compared with other states. Two official Siddha formulations, namely Kabasura Kudineer Chooranam and Nilavembu Kudineer Chooranam and novel herbal formulation – JACOM, are used to combat vector-borne diseases. These decoctions lack an evidence base as a formulation. Screening has been done to check the efficacy of the formulation in inhibiting neuraminidase. Neuraminidase inhibition assay was performed to determine the activity of Siddha formulations. The Kabasura Kudineer Chooranam, Nilavembu Kudineer Chooranam and JACOM showed excellent inhibitory activity. The Kabasura Kudineer and Nilavembu Kudineer and JACOM aqueous extract showed maximum neuraminidase inhibition of 80.35%, 91.78% and 87.97%, respectively.</p>

Screening of Influenza a (H1N1) Neuraminidase Inhibitor for Kabasura Kudineer, Nilavembu Kudineer and the Novel Formulation JACOM

<p>Due to erratic climate change, vector-borne diseases started flaring up from the second half of the last decade. Siddha medicine has been used as a public health tool to effectively manage chikungunya and dengue in the epidemics that happened in 2008 and 2016. Tamil Nadu government has made enormous efforts to control vector-borne diseases. Due to which morbidity and mortality due to vector borne diseases came down compared with other states. Two official Siddha formulations, namely Kabasura Kudineer Chooranam and Nilavembu Kudineer Chooranam and novel herbal formulation – JACOM, are used to combat vector-borne diseases. These decoctions lack an evidence base as a formulation. Screening has been done to check the efficacy of the formulation in inhibiting neuraminidase. Neuraminidase inhibition assay was performed to determine the activity of Siddha formulations. The Kabasura Kudineer Chooranam, Nilavembu Kudineer Chooranam and JACOM showed excellent inhibitory activity. The Kabasura Kudineer and Nilavembu Kudineer and JACOM aqueous extract showed maximum neuraminidase inhibition of 80.35%, 91.78% and 87.97%, respectively.</p>

Anti-Influenza Activity of an Ethyl Acetate Fraction of a Rhus verniciflua Ethanol Extract by Neuraminidase Inhibition

Antigenic mismatch can cause influenza vaccines to be ineffective, and influenza viruses resistant to antiviral drugs are rising. Thus, development of antiviral agents against these viruses is an immediate need. Rhus verniciflua (RVS) has long been used in herbal medicine and as a nutritional supplement. The effect of RVS and its components on influenza virus has not, however, been reported. We found that RVS treatment significantly reduced viral replication when evaluated with green fluorescent protein- (GFP-) tagged virus (influenza A virus, A/PR/8/34-GFP) in Madin–Darby canine kidney (MDCK) cells. RVS showed significant inhibition of neuraminidase from A/PR/8/34. Subsequently, three fractions were prepared from an ethanolic crude extract of RVS. In vitro assays indicated that an ethyl acetate fraction (RVSE) was more potent than H2O and CHCl3 fractions. RVSE significantly suppressed influenza virus infection in MDCK cells via neuraminidase inhibition. Additionally, RVSE treatment inhibited expression of several virus proteins and decreased mortality of mice exposed to influenza A/PR/8/34 by 50% and reduced weight loss by 11.5%. Active components in RVSE were isolated, and 5-deoxyluteolin (5) and sulfuretin (7) demonstrate the highest neuraminidase inhibitory activity against influenza A virus. RVS, RVSE, and their constituents may be useful for the development of anti-influenza agents.

Characterization of neuraminidase inhibitor-resistant influenza virus isolates from immunocompromised patients in the Republic of Korea

Background: The emergence of influenza viruses resistant to anti-influenza drugs is a threat to public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemic of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission. Methods: Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018-2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates. Results: Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the respiratory tract despite oseltamivir and peramivir treatment. Through the neuraminidase inhibition assay, both the viruses were found to be resistant to oseltamivir and peramivir, but not to zanamivir. Although hemagglutinin and neuraminidase phylogenetic analyses suggested that the two A(H1N1)pdm09 isolates were not identical, their antigenicity was similar to that of the 2018-19 influenza vaccine virus. Conclusions: Our data indicate the utility of monitoring influenza-infected immunocompromised patients in general hospitals for the early detection of emerging neuraminidase inhibitor-resistant viruses and maintaining continuous laboratory surveillance of patients with influenza-like illness in sentinel clinics to monitor the spread of such new variants. Finally, characterization of the virus can inform the assessment of risk for future epidemics and pandemics caused by drug-resistant influenza viruses.