scholarly journals p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein

2021 ◽  
Vol 9 (4) ◽  
Author(s):  
Athanasios Panagiotopoulos ◽  
Melpomeni Tseliou ◽  
Ioannis Karakasiliotis ◽  
Danai‐Maria Kotzampasi ◽  
Vangelis Daskalakis ◽  
...  
Keyword(s):  
Viral Replication ◽  
In Silico ◽  
Nucleocapsid Protein ◽  
Influenza A ◽  
Influenza A H1n1

scholarly journals Detailed Molecular Interactions of Favipiravir with SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza Virus Polymerases In Silico

2020 ◽  
Vol 8 (10) ◽  
pp. 1610 ◽  
Author(s):  
Mitsuru Sada ◽  
Takeshi Saraya ◽  
Haruyuki Ishii ◽  
Kaori Okayama ◽  
Yuriko Hayashi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Molecular Interactions ◽  
In Silico ◽  
Influenza A ◽  
Active Sites ◽  
Active Form ◽  
Antiviral Drug ◽  
Virus Rna ◽  
Influenza A H1n1 ◽  
In Silico Studies

Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5′-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses.

scholarly journals Immune Activation and Viral Replication after Vaccination with an Influenza A H1N1 2009 Vaccine in HIV-Infected Children Receiving Antiretroviral Therapy

2013 ◽  
Vol 35 ◽  
pp. 221-227 ◽  
Author(s):  
Nattawat Onlamoon ◽  
Petai Unpol ◽  
Michittra Boonchan ◽  
Kasama Sukapirom ◽  
Orasri Wittawatmongkol ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Viral Replication ◽  
Cd8 T Cells ◽  
Immune Activation ◽  
Influenza A ◽  
Haemagglutination Inhibition ◽  
Hla Dr ◽  
Influenza A H1n1 ◽  
The Impact

Immunization with a pandemic influenza A H1N1 2009 was recommended for HIV-infected patients. However, there is limited information concerning the impact of immunization with this vaccine on immune activation and HIV viral replication. In this study, 45 HIV-infected children and adolescents receiving antiretroviral therapy were immunized with a 2-dose series of nonadjuvated monovalent influenza A H1N1 2009 vaccine upon enrollment and approximately 1 month later. Immunogenicity was determined by haemagglutination inhibition assay. The level of immune activation was determined by identification of CD38 and HLA-DR on CD8+ T cells. Patients were divided into 2 groups which include patients who had an undetectable HIV viral load (HIV detectable group) and patients who show virological failure (HIV nondetectable group). The results showed seroconversion rate of 55.2% in HIV nondetectable group, whereas 31.3% was found in HIV detectable group. Both groups of patients showed no major increase in immune activation after immunization. Interestingly, a decrease in the frequency of CD8+ T cells that coexpressed CD38 and HLA-DR was observed after immunization in both groups of patients. We suggested that immunization with influenza A H1N1 2009 vaccine can induce immune response to the pandemic virus without major impact on HIV viral replication and immune activation.

In vitro Inhibitory Effects of Combinations of anti-Influenza Agents

1995 ◽  
Vol 6 (2) ◽  
pp. 109-113 ◽  
Author(s):  
L. K. Madren ◽  
C. Shipman ◽  
F. G. Hayden
Keyword(s):  
Viral Replication ◽  
Influenza A ◽  
H1n1 Virus ◽  
Mdck Cells ◽  
Clinical Isolates ◽  
H1n1 Subtype ◽  
Additive Effects ◽  
Inhibitory Effects ◽  
Influenza A H1n1

To assess the possible interactions among candidate anti-influenza agents, dual combinations of rimantadine, ribavirin, 2′-deoxy-2′-fluoroguanosine (2-FDG) and 4-guanidino-Neu5Ac2en (GG167) were tested against clinical isolates of influenza A H3N2 and H1N1 subtype viruses in MDCK cells by ELISA. Each of the dual combinations showed additive effects, except for the combination of 2-FDG and ribavirin which was synergistic against the influenza A (H1N1) virus. However, this combination also showed enhanced cytotoxicity. In this assay system, influenza agents with differing mechanisms of antiviral interaction interacted in an additive fashion with respect to inhibition of viral replication.

scholarly journals The Entry Blocker Peptide Produced in Chlamydomonas reinhardtii Inhibits Influenza Viral Replication in vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Karen Lizbeth Reyes-Barrera ◽  
Ruth Elena Soria-Guerra ◽  
Rogelio López-Martínez ◽  
Leonor Huerta ◽  
Nohemí Salinas-Jazmín ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Replication ◽  
Chlamydomonas Reinhardtii ◽  
Synthetic Peptide ◽  
Influenza A ◽  
Total Soluble Protein ◽  
Entry Blocker ◽  
Influenza A H1n1 ◽  
Eb Peptide

This year, a respiratory virus caused an emergency pandemic alert in health services around the world, showing the need for biotechnological approaches to fight these diseases. The influenza virus is one of the main viral agents that generate pandemic outbreaks. Currently, the majority of co-circulating influenza A virus (IAV) strains are adamantine‐ and oseltamivir-resistant strains, and the challenge is to find new antivirals for more efficient treatments. The antiviral entry blocker (EB) peptide is a promising candidate for blocking the virus entry into cells. The aim of this research was to express the EB peptide in the microalgae Chlamydomonas reinhardtii and test its antiviral activity against IAV in vitro. The EB peptide nucleotide sequence was introduced into the nuclear genome of microalgae using Agrobacterium tumefaciens transformation. The EB peptide amount produced in transformed microalgae was 4.99 ± 0.067% of the total soluble protein. In hemagglutination inhibition assays using influenza A/H1N1 pdm and influenza A H1N1/Virginia/ATCC/2009 strains, we reported that the EB peptide extract from the microalgae showed 100-fold higher efficiency than the EB synthetic peptide. In addition, both the EB peptide extract and synthetic peptide inhibited viral replication in MDCK cells (IC50 = 20.7 nM and IC50 = 754.4 nM, respectively); however, the EB peptide extract showed a 32-fold higher antiviral effectiveness than the synthetic peptide against influenza A/H1N1 pdm. Extracts from untransformed and transformed microalgae and synthetic peptide did not show cytotoxic effect on MDCK cell monolayers. Thus, C. reinhardtii may be a fast, safe, and effective expression platform for production of peptides with significant antiviral activity and can be used as a prophylactic treatment to reduce viral propagation.

scholarly journals Structure-Guided Creation of an Anti-HA Stalk Antibody F11 Derivative That Neutralizes Both F11-Sensitive and -Resistant Influenza A(H1N1)pdm09 Viruses

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1733
Author(s):  
Osamu Kotani ◽  
Yasushi Suzuki ◽  
Shinji Saito ◽  
Akira Ainai ◽  
Akira Ueno ◽  
...  
Keyword(s):  
In Silico ◽  
Influenza A ◽  
Proteolytic Cleavage ◽  
Structural Basis ◽  
Virus Envelope ◽  
Fab Fragment ◽  
Influenza A H1n1 ◽  
Critical Residue ◽  
Stalk Domain ◽  
Conformational Rearrangements

The stalk domain of influenza virus envelope glycoprotein hemagglutinin (HA) constitutes the axis connecting the head and transmembrane domains, and plays pivotal roles in conformational rearrangements of HA for virus infection. Here we characterized molecular interactions between the anti-HA stalk neutralization antibody F11 and influenza A(H1N1)pdm09 HA to understand the structural basis of the actions and modifications of this antibody. In silico structural analyses using a model of the trimeric HA ectodomain indicated that the F11 Fab fragment has physicochemical properties, allowing it to crosslink two HA monomers by binding to a region near the proteolytic cleavage site of the stalk domain. Interestingly, the F11 binding allosterically caused a marked suppression of the structural dynamics of the HA cleavage loop and flanking regions. Structure-guided mutagenesis of the F11 antibody revealed a critical residue in the F11 light chain for the F11-mediated neutralization. Finally, the mutagenesis led to identification of a unique F11 derivative that can neutralize both F11-sensitive and F11-resistant A(H1N1)pdm09 viruses. These results raise the possibility that F11 sterically and physically disturbs proteolytic cleavage of HA for the ordered conformational rearrangements and suggest that in silico guiding experiments can be useful to create anti-HA stalk antibodies with new phenotypes.

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