The impact of targeted local outreach clinics to improve COVID-19 vaccine uptake: controlled interrupted time series in South West England.

Background: Outreach clinics were part of efforts to maximise uptake in COVID-19 vaccination.

Methods: We used controlled interrupted time series, matching on age, sex, deprivation and vaccination eligibility date, to determine the effect of outreach clinics on time to first COVID-19 vaccine, using a population-based electronic health record database of 914,478 people, from December 2020 to December 2021; people living within 1 mile of each outreach clinics were exposed.

Results: 50% of 288,473 exposed citizens were white British, and 71% were aged 0-49 years.

Kinetic comparison of all eleven viral polyprotein cleavage site processing events by SARS-CoV-2 main protease using a linked protein FRET platform.

The main protease (M) remains an essential therapeutic target for COVID-19 post infection intervention given its critical role in processing the majority of viral proteins encoded by the genome of severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2). Upon viral entry, the +ssRNA genome is translated into two long polyproteins (pp1a or the frameshift-dependent pp1ab) containing all the nonstructural proteins (nsps) required by the virus for immune modulation, replication, and ultimately, virion assembly. Included among these nsps is the cysteine protease M (nsp5) which self-excises from the polyprotein, dimerizes, then sequentially cleaves 11 of the 15 cut-site junctions found between each nsp within the polyprotein.

Inequality in uptake of bowel cancer screening by deprivation, ethnicity and smoking status: cross-sectional study in 86 850 citizens.

Background: Survival from colorectal cancer depends on stage at detection. In England, bowel cancer mortality has historically been highest in deprived areas. During the initial stages of the COVID-19 pandemic, it was necessary to temporarily halt many screening programmes, which may have led to inequalities in uptake since screening restarted.

A novel class of broad-spectrum active-site-directed 3C-like protease inhibitors with nanomolar antiviral activity against highly immune-evasive SARS-CoV-2 Omicron subvariants.

Antivirals with broad coronavirus activity are important for treating high-risk individuals exposed to the constantly evolving SARS-CoV-2 variants of concern (VOCs) as well as emerging drug-resistant variants. We developed and characterized a novel class of active-site-directed 3-chymotrypsin-like protease (3CLpro) inhibitors (). Our lead direct-acting antiviral (DAA), , is a non-covalent, non-peptide with a dissociation constant of 170 nM against recombinant SARS-CoV-2 3CLpro.