ABSTRACT
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.
ABSTRACT
The College of New Jerseys Chemistry Department and School of Science have been strategically transforming our teaching, learning, and mentoring environments for over a decade through programs that are targeted toward new majority students: low-income, first generation, and historically marginalized races and ethnicities. Recently, we shifted from programs that target a small number of students to focus on systemic and structural changes to create inclusive excellence. We formalized our work in a Theory of Change (ToC) that emphasizes mechanisms for our faculty to depart from traditional pedagogy to become experimentalist teachers who use evidence-based practices and data to support our student success. The ToC is built on three pillars: (1) gaining empathy and understanding of our students, (2) a changing toolkit of acceptable pedagogical practices, and (3) a process to create shared language and values and an understanding of our responsibilities to our students. By focusing on mechanism, we do not prescribe a single pedagogy but instead are flexible for different course contexts. Department work on the ToC allowed our faculty to pivot instead of panic during the shift to online instruction. The students noted smooth transitions to remote learning, and more importantly, departmental discussions regarding pedagogy helped faculty to support each other with suggestions and sharing of best practices. As a department, we learned a great deal during the pandemic that furthers our collective work toward inclusive excellence and believe our ToC is transferable to other institutions.
ABSTRACT
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) (â¼200 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 (â¼50 pN) might play a role in the increasing spread of COVID-19.