Supramolecular Nanofibers Block SARS-CoV-2 Entry into Human Host Cells.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) on host cells to initiate cellular entry. Blocking the interactions between the spike protein and ACE2 offers promising therapeutic opportunities to prevent infection. We report here on peptide amphiphile supramolecular nanofibers that display a sequence from ACE2 in order to promote interactions with the SARS-CoV-2 spike receptor binding domain. We demonstrate that displaying this sequence on the surface of supramolecular assemblies preserves its α-helical conformation and blocks the entry of a pseudovirus and its two variants into human host cells. We also found that the chemical stability of the bioactive structures was enhanced in the supramolecular environment relative to the unassembled peptide molecules. These findings reveal unique advantages of supramolecular peptide therapies to prevent viral infections and more broadly for other targets as well.

Principles Learned from the International Race to Develop a Safe and Effective COVID-19 Vaccine.

Vaccines against COVID-19 have the potential to protect people before they are exposed to the infective form of the virus. However, because of the involvement of pathogenic immune processes in many severe presentations of COVID-19, eliciting an immune response with a vaccine must strike a delicate balance to achieve viral clearance without also inducing immune-mediated harm. This Outlook synthesizes current laboratory findings to define which parts of the immune system help with recovery from and protection against the virus and which can lead to adverse outcomes. To inform our understanding, we analyze research about the immune mechanisms implicated in SARS-CoV, from the 2003 outbreak, and SARS-CoV-2, the virus causing COVID-19. The impact of how innate immunity, humoral immunity, and cell-mediated immunity play a role in a harmful versus helpful response is discussed, establishing principles to guide the development and evaluation of a safe but effective COVID-19 vaccine. The principles derived include (i) targeting the appropriate specificity and effector function of the humoral response, (ii) eliciting a T cell response, especially a cytotoxic T cell response, to achieve safe, yet effective, immune protection from COVID-19, and (iii) monitoring for the possibility of acute lung injury during SARS-CoV-2 infection post-vaccination in preclinical and clinical studies. These principles can not only guide efforts toward a safe and effective COVID-19 vaccine, but also the development of effective vaccines for viral pandemics to come.