Benefits and Challenges of Using Virtual Primary Care During the COVID-19 Pandemic: From Key Lessons to a Framework for Implementation (preprint)

Background: With the onset of COVID-19, general practitioners (GPs) and patients worldwide swiftly transitioned from face-to-face to digital remote consultations. There is a need to evaluate how this global shift has impacted patient care, healthcare providers, patient and carer experience, and health systems. Objective: We explored GPs' perspectives on the main benefits and challenges of using digital remote care. Methods: GPs across 20 countries completed an online questionnaire between June - September 2020. GPs' perceptions on main barriers and challenges were explored using free-text questions. Thematic analysis was used to analyse the data. Results: 1,605 respondents participated in our survey. The benefits identified included reducing COVID-19 transmission risks, guaranteeing access and continuity of care, improved efficiency, faster access to care, improved convenience and communication with patients, greater work flexibility for providers, and hastening the digital transformation of primary care and the accompanying legal frameworks. Main challenges included patient's preference for face-to-face consultations, digital exclusion, lack of physical examinations, clinical uncertainty, delays in diagnosis and treatment, overuse and misuse of digital remote care, and unsuitability for certain types of consultations. Other challenges include the lack of formal guidance, higher workloads, remuneration issues, organisational culture, technical difficulties, implementation and financial issues, and regulatory weaknesses. Conclusion: At the frontline of care delivery, GPs can provide important insights on what worked well, why, and how. Lessons learned during the emergency phase can be used to inform the stable adoption of virtual care solutions, and co-design processes and platforms that are technologically robust, secure, and supported by a strategic long-term plan.

Discovery of a Novel Inhibitor of Coronavirus 3CL Protease as a Clinical Candidate for the Potential Treatment of COVID-19 (preprint)

COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential to the viral life cycle across a broad spectrum of coronaviruses with no close human analogs. The designed phosphate prodrug PF-07304814 is metabolized to PF-00835321 which is a potent inhibitor in vitro of the coronavirus family 3CL pro, with selectivity over human host protease targets. Furthermore, PF-00835231 exhibits potent in vitro antiviral activity against SARS-CoV-2 as a single agent and it is additive/synergistic in combination with remdesivir. We present the ADME, safety, and in vitro antiviral activity data to warrant clinical evaluation. One Sentence SummaryThe phosphate prodrug PF-07304814 is disclosed as an investigational novel intravenous small molecule 3CL protease inhibitor for COVID-19.

The Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19 (preprint)

The novel coronavirus disease COVID-19 that emerged in 2019 is caused by the virus SARS CoV-2 and named for its close genetic similarity to SARS CoV-1 that caused severe acute respiratory syndrome (SARS) in 2002. Both SARS coronavirus genomes encode two overlapping large polyproteins which are cleaved at specific sites by a cysteine 3C-like protease (3CLpro) in a post-translational processing step that is critical for coronavirus replication. The 3CLpro sequences for CoV-1 and CoV-2 viruses are 100% identical in the catalytic domain that carries out protein cleavage. A research effort that focused on the discovery of reversible and irreversible ketone-based inhibitors of SARS CoV-1 3CLpro employing ligand-protease structures solved by X-ray crystallography led to the identification of 3 and 4. Preclinical experiments reveal 4 (PF-00835231) as a potent inhibitor of CoV-2 3CLpro with suitable pharmaceutical properties to warrant further development as an intravenous treatment for COVID-19.