Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies

Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.

Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart

Adverse cardiac events are a common complication of viral and bacterial pneumonia. For over a century, it has been recognized that influenza infection promotes severe forms of pulmonary disease mainly caused by the bacterium Streptococcus pneumoniae .

Impact of COVID-19 on Wages of the Labours in India

We know about Plague Pandemic, Cholera Pandemic, Influenza Pandemic and the most recent Covid-19 Pandemic. The Covid-19 pandemic is world’s one of the dangerous human calamities. In the year 2020, Covid-19 have impacted human lives and survival in various ways. One of the ways in which Covid-19 have impacted on human lives in affecting the wages of labour in India. Due to the Covid-19 pandemic, India went under a lockdown condition for over three months. This lockdown has created a big depreciative influence on the economy which eventually impacted on business and their labours. In the year 2020 during second wave of Covid-19, over 10 million people lost their jobs and 97 percent households in the country have witnessed decline in incomes. The government is working hard to recover the loss as well as to secure the lives in the country.

TreeKnit: Inferring Ancestral Reassortment Graphs of influenza viruses

When two influenza viruses co-infect the same cell, they can exchange genome segments in a process known as reassortment. Reassortment is an important source of genetic diversity and is known to have been involved in the emergence of most pandemic influenza strains. However, because of the difficulty in identifying reassortments events from viral sequence data, little is known about its role in the evolution of the seasonal influenza viruses. Here we introduce TreeKnit, a method that infers ancestral reassortment graphs (ARG) from two segment trees. It is based on topological differences between trees, and proceeds in a greedy fashion by finding regions that are compatible in the two trees. Using simulated genealogies with reassortments, we show that TreeKnit performs well in a wide range of settings and that it is as accurate as a more principled bayesian method, while being orders of magnitude faster. Finally, we show that it is possible to use the inferred ARG to better resolve segment trees and to construct more informative visualizations of reassortments.

The Pandemic Influenza Preparedness Framework as a ‘specialized international access and benefit-sharing instrument’ under the Nagoya Protocol

The World Health Organization (WHO) is starting to come to terms with the public health implications of the United Nations’ Convention on Biological Diversity (CBD) and its supplementary Nagoya Protocol about genetic resource access and benefit-sharing (ABS). Since 2017 there have been calls to recognize the WHO’s Pandemic Influenza Preparedness (PIP) Framework as a specialized international ABS instrument under the Nagoya Protocol. This article will examine whether the PIP Framework meets the criteria of a specialized international ABS instrument as laid out in a 2018 study commissioned by the Subsidiary Body on Implementation to the CBD (CBD/SBI/2/INF/17). Our analysis concludes that while the PIP Framework meets the specialization criteria, it fails to meet the supportiveness criteria and does not provide legal certainty for pandemic influenza virus ABS. Furthermore, we demonstrate that recognition of the PIP Framework as a specialized instrument would not mean that the CBD and Nagoya Protocol no longer apply to influenza viruses with human pandemic potential as has been asserted, rendering the relationship between the three international agreements unclear. As the WHO grapples with how to regulate access to other (non-influenza) human pathogens and the fair and equitable sharing of benefits associated with their use, a full appreciation of what ABS means when applied to pathogens is essential.

Influenza

The influenza virus is a segmented RNA virus with different mechanisms for mutations, and hence for minor (antigenic drift) and major (antigenic shift) changes. Influenza virus A was responsible for pandemics on average every 30 years in the past, with the most recent being the 2009 swine-origin influenza A H1N1 (SO-H1N1). The clinical picture is unspecific: seasonal or pandemic influenza cannot be differentiated from other viral respiratory infections on clinical grounds. PCR has become the standard for microbiological confirmation of the diagnosis. Treatment options remain limited with neuraminidase inhibitors (oseltamivir; zanamivir). Resistance may occur under treatment or under prophylaxis; however, it is still rare overall. Vaccination is still the preferred method for prevention. However, the long lead time for production (at least 6 months) poses a challenge. Innovative new techniques like cell culture or recombinant productions are urgently needed. Pandemic influenza vaccines for SO-H1N1 were shown to be effective and safe in children, pregnant women, adults, and also in elderly. Pre-pandemic vaccines (H5N1) are also available.