https://www.dora.lib4ri.ch/psi/islandora/object/psi%3A34683/datastream/PDF/Gao-2021-Crystal_structure_of_SARS-CoV-2_papain-like_protease-%28published_version%29.pdf

Crystal structure of SARS-CoV-2 papain-like protease.

Impact of Famotidine Use on Clinical Outcomes of Hospitalized Patients With COVID-19.

COVID-19 was initially considered to be a respiratory disease but soon after the pandemic established it became clear that the SARS-CoV-2 virus which caused the disease could lead to serious systemic consequences affecting most of the major organs including the digestive tract, liver and pancreas. This review brings together the new information which is clinically relevant to the gastroenterologist including the origins of the disease, mechanisms of tissue damage and how this affects specific patient groups, including those with inflammatory bowel disease, comorbidities and the role of immunosuppression, chronic liver disease and the risk of decompensation for those with cirrhosis. The impact of COVID-19 for gastrointestinal emergencies is addressed together with the implications for the conduct of endoscopic and other interventional and diagnostic procedures. The importance of fully understanding the pharmacology and therapeutic implications of drugs commonly used by the gastroenterologist and their relationship with COVID-19 are also highlighted. The risk for drug-drug interactions is considerable in patients seriously ill with COVID-19 who are often requiring mechanical ventilation and life-support. Some re-purposed drugs used against SARS-CoV-2 can cause or aggravate some of the COVID-19 GI symptoms and also can induce iatrogenic liver injury. Ongoing clinical studies will hopefully identify effective drugs with a risk-benefit ratio which will be more favorable than many recently tried treatments.

/pdf/covid-19-and-gastrointestinal-disease-implications-for-the-204re4c922.pdf

COVID-19 and Gastrointestinal Disease. Implications for the Gastroenterologist.

Recent advances in management of COVID-19: A review.

Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection.

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. SARS-CoV-2 infection is necessary but not sufficient for development of clinical COVID-19 disease. Currently, there are no approved pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We have investigated several plausible hypotheses for famotidine activity including antiviral and host-mediated mechanisms of action. We propose that the principal mechanism of action of famotidine for relieving COVID-19 symptoms involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release. Based on these findings and associated hypothesis, new COVID-19 multi-drug treatment strategies based on repurposing well-characterized drugs are being developed and clinically tested, and many of these drugs are available worldwide in inexpensive generic oral forms suitable for both outpatient and inpatient treatment of COVID-19 disease.

/pdf/covid-19-famotidine-histamine-mast-cells-and-mechanisms-1bq9couen3.pdf

COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We explore several plausible avenues of activity including antiviral and host-mediated actions. We propose that the principal famotidine mechanism of action for COVID-19 involves on-target histamine receptor H 2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release.

/pdf/covid-19-famotidine-histamine-mast-cells-and-mechanisms-2scdncddtt.pdf

Nora Smith

Papers

COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms

COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms

Models for COVID-19 Early Cardiac Pathology Following SARS-CoV-2 Infection.