Search for: All records

The novel coronavirus disease 2019 (COVID-19) pandemic has disrupted modern societies and their economies. The resurgence in COVID-19 cases as part of the second wave is observed across Europe and the Americas. The scientific response has enabled a complete structural characterization of the Severe Acute Respiratory Syndrome—novel Coronavirus 2 (SARS-CoV-2). Among the most relevant proteins required by the novel coronavirus to facilitate the cell entry mechanism is the spike protein. This protein possesses a receptor-binding domain (RBD) that binds the cellular angiotensin-converting enzyme 2 (ACE2) and then triggers the fusion of viral and host cell membranes. In this regard, a comprehensive characterization of the structural stability of the spike protein is a crucial step to find new therapeutics to interrupt the process of recognition. On the other hand, it has been suggested that the participation of more than one RBD is a possible mechanism to enhance cell entry. Here, we discuss the protein structural stability based on the computational determination of the dynamic contact map and the energetic difference of the spike protein conformations via the mapping of the hydration free energy by the Poisson–Boltzmann method. We expect our result to foster the discussion of the number of RBD involved during recognition and the repurposing of new drugs to disable the recognition by discovering new hotspots for drug targets apart from the flexible loop in the RBD that binds the ACE2. 

We report on the novel observation about the gain in nanomechanical stability of the SARS-CoV-2 (CoV2) spike (S) protein in comparison with SARS-CoV from 2002 (CoV1). Our findings have several biological implications in the subfamily of coronaviruses, as they suggest that the receptor binding domain (RBD) (∼200 amino acids) plays a fundamental role as a damping element of the massive viral particle's motion prior to cell-recognition, while also facilitating viral attachment, fusion and entry. The mechanical stability via pulling of the RBD is 250 pN and 200 pN for CoV2 and CoV1 respectively, and the additional stability observed for CoV2 (∼50 pN) might play a role in the increasing spread of COVID-19.