Differences in New Variant of Concern Replication at Physiological Temperatures In Vitro.

Using multiple cell types and isolates of Delta and Omicron variants of SARS-CoV-2, we report differences in virus production, replication, and infectivity in vitro. Ancestral and Delta SARS-CoV-2 variant exhibit reduced virus production and replication at 34°C compared to 37°C while Omicron replication is balanced between temperatures.

South African (501Y.V2) and the United Kingdom (B.1.1.7) SARS-CoV-2 spike (S) protein variants demonstrate a higher binding affinity to ACE2.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affects the lower respiratory tract by binding to angiotensin-converting enzyme 2 (ACE2) via its S-protein. Recent emerging SARS-CoV-2 variants from the United Kingdom (B.1.1.7) and South Africa (501Y.V2) are spreading worldwide at an alarming rate. The new variants have manifested amino acid substitution K417N, E484K and N501Y on the RBD domain that binds to ACE2. As such, these mutations may influence the binding of the S-protein to ACE2 and affect viral entry into the host cell. Methods In this study, we modelled the amino acids substitutions on the S-protein and utilised HADDOCK server to assess the S-protein RBD domain binding with ACE2. Additionally, we calculated the binding affinity of ACE2 to S-protein WT, B.1.1.7 and 501Y.V2 variants using Molecular Mechanics-Generalized Born Surface Area (MM/GBSA). Results We demonstrate that the S-protein of both variants possesses higher binding affinity to ACE2 than WT, with the South African 501Y.V2 is a more infective strain than the B.1.1.7 that originated in the United Kingdom. Conclusion The South African 501Y.V2 variant presents three amino acid substitutions that changed the H-bonding network resulting in a higher affinity to ACE2, indicating that the 501Y.V2 strain is more infective than the B.1.1.7 strain.

Immunogenomics guided design of immunomodulatory multi-epitope subunit vaccine against the SARS-CoV-2 new variants, and its validation through in silico cloning and immune simulation.

Reports of the novel and more contagious strains of SARS-CoV-2 originating in different countries have further aggravated the pandemic situation. The recent substitutions in spike protein may be critical for the virus to evade the host's immune system and therapeutics that have already been developed. Thus, this study has employed an immunoinformatics pipeline to target the spike protein of this novel strain to construct an immunogenic epitope (CTL, HTL, and B cell) vaccine against the new variant. Our investigation revealed that 12 different epitopes imparted a critical role in immune response induction. This was validated by an exploration of physiochemical properties and experimental feasibility. In silico and host immune simulation confirmed the expression and induction of both primary and secondary immune factors such as IL, cytokines, and antibodies. The current study warrants further lab experiments to demonstrate its efficacy and safety.

The new UK SARS-CoV-2 variant and lockdown - causes and consequences.

The new variant of concern (VOC), B.1.1.7, has a distinct set of mutations in nucleotides encoding the spike (S) protein on the surface of SARS-CoV-2. SARS-CoV-2 previously accumulated mutations at a much slower rate, of 1-2 per month; the sudden appearance of a large cluster of mutations was thought to be unusual. We now suspect that VOC may have arisen from immunosuppressed individuals who shed virus for longer periods. Epidemiological analyses estimate VOC to be more infectious; this is of most concern because these estimates were calculated during periods where many regions of the UK were in high social distancing restrictions. Therefore, the previous 'tiered' system implemented in the UK was ineffective at containing VOC. The most likely reason for this is that previous restrictions, no matter how strict, still allowed for gatherings in certain places. VOC also has implications for the national vaccination programme - a higher proportion of people will need to be vaccinated with a more infectious virus. Prolongation of the second dose of vaccines to increase vaccine uptake has understandably caused concern, but is based on sound immunological principles. There is now an urgent need to monitor the effect of new variants on vaccine efficacy - marking a new chapter in the global fight against COVID-19.