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.
Highlights
Previous outbreaks of coronaviruses have threatened our modern societies [1,2]
angiotensin-converting enzyme 2 (ACE2), our study renders the open state less stable than the closed state which agrees with the singlemolecule Förster Resonance Energy Transfer (smFRET) study [34] that identifies the closed state as the most populated state which the smFRET study that identifies the closedstructural state as thestability most populated state in in the agrees lack ofwith study shows an additional associated with the lack of our study shows an additional structural stability associated with almost almost twice more high-frequency contacts in 1up12own than 2up1down conformations
We expect that our structural and energetic studies can provide additional information regarding the space of interactions mapped by certain key residues that are crucial for stabilization of the spike protein during an apparent dynamic equilibrium mediated by transitions from close to open conformations prior to ACE2 recognition
Summary
Previous outbreaks of coronaviruses have threatened our modern societies [1,2]. neither of them stressed the worldwide health system and economy [3] more than the novel coronavirus.As of 30 October 2020, almost 45 million confirmed cases with a death toll over one million around the world have been reported. Previous outbreaks of coronaviruses have threatened our modern societies [1,2]. Neither of them stressed the worldwide health system and economy [3] more than the novel coronavirus. As of 30 October 2020, almost 45 million confirmed cases with a death toll over one million around the world have been reported. There is an urgent need to understand the molecular features of each of the proteins that are assembled into the virion. The fast spread of COVID-19 around the globe urges to devise viral deactivation strategies prior to cell recognition or block the viral replication mechanism, among others [4]. A key component in all coronavirus associated with cell entry is the Materials 2020, 13, 5362; doi:10.3390/ma13235362 www.mdpi.com/journal/materials
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