COVID19 s cytokine storm ushers in a local complement storm in the lungs
A new study published in the journal
Science Immunology analyzed lung epithelial cells from patients infected with COVID-19 and found the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces the complement system as a dangerous weapon for viral infection.
The complement system is an extension of the innate immune system to recognize pathogens and remove them. Prior research has shown a correlation between severe COVID-19 infection and high levels of complement.
The mechanism of action is driving the JAK1/2-dependent local complement hyperactivation. Using the JAK1/2 inhibitor ruxolitinib alone or with remdesivir normalized interferon signature genes inhibited the C3a protein of the complement system created from infected lung cells.
Small molecule inhibitors of SARS-CoV-2 identified by screening
Even as the vaccine rollout continues against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seeking to bring an end to the coronavirus disease 2019 (COVID-19) pandemic, new variants emerge that show immune escape capabilities. Effective and safe drugs thus remain essential to treat severe infections with this virus.
A new preprint, released on the
bioRxiv server, describes the identification of small molecule inhibitors that block the catalytic activity of the crucial viral non-structural protein 5 (nsp5), using a large-scale screening method.
The importance of nsp5
At least nine enzymes of the virus are important for viral proliferation and are thus ideal for the development of antiviral drugs. These enzymes have the same sequence between different coronaviruses, unlike the spike, nucleocapsid and other structural proteins that are less conserved. This makes vaccines based on the latter protei
Researchers provide ultrastructural details of SARS-CoV-2-infected respiratory epithelial cells
A team of scientists from the United Kingdom recently investigated the ultrastructural details of the attachment, entry, and budding processes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the human airway epithelium. They have used a highly differentiated air-liquid interface cultures of airway epithelium to thoroughly investigate the viral infection cycle. The study is currently available on the
Background
SARS-CoV-2, the causative pathogen of coronavirus disease 2019 (COVID-19), is an enveloped RNA virus belonging to the Coronaviridae family. The virus primarily attacks human airway epithelial cells to initiate infection. Mechanistically, the receptor-binding domain (RBD) of the S1 subunit of the viral spike glycoprotein binds to angiotensin-converting enzyme 2 (ACE2), which is ubiquitously expressed at the apical surface of host airway epithelial cells. This is
Many different variants and lineages have arisen from the ancestral Wuhan-Hu1 strain of the SARS-CoV-2. This requires careful attention to control measures since many are more infective and transmissible than the older strains. A recent study compares the UK variant of this virus with the wildtype in terms of susceptibility to routine cleaning and disinfection measures.
South Africa SARS-CoV-2 variant B.1.351 easily escapes Sputnik vaccine
The current pandemic of novel coronavirus disease 2019 (COVID-19) was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has undergone numerous mutations in its genome to emerge as different variants. As of now, a dozen vaccines have received emergency use authorization, and many countries around the world have initiated mass vaccination campaigns.
A new preprint research paper posted to the
medRxiv server reports on vaccine resistance data that pushes the end of the pandemic further away.
Variants of concern and spike mutations
Most vaccines now in use or being developed focus on generating antibodies to the viral spike protein, which mediates host cell entry and infection. This is based on the strong correlation between neutralizing antibodies to the spike and protective immunity.