The prestigious Journal of Biological Chemistry has recently published a review and hypothesis on SARS-CoV-2 by the researcher Pablo Fuentes Prior, coordinator of the Molecular Bases of Disease research group at the Sant Pau Research Institute -IIB Sant Pau.
The Covid-19 pandemic has already caused more than one million deaths worldwide, and this death toll will be much higher before effective treatments and vaccines become available. The causative agent of the disease, the SARS-CoV-2 coronavirus, shows important similarities to the previously emerged SARS-CoV-1, but also striking differences. First, SARS-CoV-2 has a significantly higher transmission and infectivity rate than SARS-CoV-1 and has infected more than 60 million people in a few months. Moreover, Covid-19 is systemic in nature, affecting not only the lungs but also the heart, liver and kidneys among other organs of patients, and causing frequent thrombotic and neurological complications. In fact, the term “viral sepsis” has recently been coined to describe its observations.
The paper “Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and Systemic Covid-19 infection” by researcher Pablo Fuentes Prior is a review of current information on the structure-function of the virus spike protein and the process of membrane fusion to provide plausible explanations for these observations. The hypothesis formulated is that several membrane-associated serine proteases (MASPs), in collaboration with or substitution of TMPRSS2, contribute to the activation of the SARS-CoV-2 spike protein. The relative concentrations of the affection receptor, ACE2, MASPs, their endogenous inhibitors (the Kunitz-type transmembrane inhibitors HAI-1/SPINT1 and HAI-2/SPINT2, as well as the major circulating Serpin) would determine the rate of host cell infection. The exclusive or predominant expression of major MASPs in specific human organs suggests a direct role of these proteins in, for example, cardiac infection and myocardial injury, liver dysfunction, renal damage, as well as neurological complications. A thorough consideration of these factors could have a positive impact on the control of the current Covid-19 pandemic.
