Abstract
The public health has declared an international state of emergency due to the spread of a new coronavirus (SARS-CoV-2) representing a real pandemic threat so that to find potential therapeutic agents is a dire need. To this aim, the SARS-CoV-2 spike (S) glycoprotein represents a crucial target for vaccines, therapeutic antibodies, and diagnostics. Since virus binding to ACE-2 alone could not be sufficient to justify such severe infection, in order to facilitate medical countermeasure development and to search for new targets, two further regions of S protein have been taken into consideration here. One is represented by the recently identified ganglioside binding site, exactly localized in our study in the galectin-like domain, and the other one by the putative integrin binding sites contained in the RBD. We propose that a cooperating therapy using inhibitors against multiple targets altogether i.e., ACE2, integrins and sugars could be definitely more effective.
Highlights
The novel coronavirus SARS-CoV-2, whose infection is associated to a respiratory syndrome with impaired lung and alveolar function, can lead to acute respiratory failure and even death (Kanduca and Shoenfeldb, 2020; Wrapp et al, 2020) so to be declared as a Public Health Emergency of International Concern by the World Health Organization.The novel virus belongs to the betacoronavirus genus, but differently from other less pathogenic human CoVs such as HCoV-OC43 and HCoV-229E, it has a strong pathogenicity that leads to death.So far the molecular bases and the mechanism that link SARS-CoV-2 coronavirus infection to the pulmonary pathology are still unexplored (Tai et al, 2020).HCoVs are positive-sense, single-stranded RNA viruses and 30,000 bp long
We focused on further emerging novel spike protein targets, such as receptors belonging to the family of integrins or sialic-acid-containing cell surface structures, considering that sialic acids linked to glycoproteins and gangliosides as well as integrins are employed by a wide spectrum of viruses, including coronaviruses, as receptors and/or attachment factors for cell entry (Wei et al, 2014; Matrosovich et al, 2015; Teoh et al, 2015)
Our idea is that these emerging new spike targets above cited can be reasonably justified by the fact that, as it is well- known, the S of coronaviruses are defined as some of the biggest viral spike glycoproteins known, so it is plausible to imagine that different domains within a single S protein could interact with various receptors rendering easier and faster the entry of the virus
Summary
The public health has declared an international state of emergency due to the spread of a new coronavirus (SARS-CoV-2) representing a real pandemic threat so that to find potential therapeutic agents is a dire need. To this aim, the SARS-CoV-2 spike (S) glycoprotein represents a crucial target for vaccines, therapeutic antibodies, and diagnostics. Since virus binding to ACE-2 alone could not be sufficient to justify such severe infection, in order to facilitate medical countermeasure development and to search for new targets, two further regions of S protein have been taken into consideration here. We propose that a cooperating therapy using inhibitors against multiple targets altogether i.e., ACE2, integrins and sugars could be definitely more effective
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
