Antibody Dependent Enhancement (ADE) is a phenomenon in which viral particles bind to virus-specific antibodies, enhancing their uptake by host cells and resulting in increased viral replication and infection. First discovered while studying dengue virus (DENV) in primates, ADE can be explained by two general mechanisms, depending on the type of virus involved. In DENV infection, ADE manifests as largely different reactivity upon secondary infection with a cross-reactive serotype and this information provides a large implication to the authorization of DENGVAXIA vaccine use. Looking into the need of vaccines considering the current SARS-CoV-2 pandemic, authors are providing a review of current knowledge correlating SARS-CoV-2 and ADE phenomenon. Using SARS-CoV-1 as a model, we can hypothesize the possible ADE pathway in SAR- CoV-2. The S protein binds to the ACE2 receptor on the host cell and triggers different immune responses depending on the titer of antibodies present. Despite in vitro studies suggesting some cross-reactivity of some antibodies generated in response to other coronaviruses to SARS-CoV-2, ADE does not appear to be a major concern in vivo. Similarly with vaccines, although there may be variation in efficacy to respective strains of SARS-CoV-2 there does not appear to be serious concern for ADE due to vaccination.

Reactive oxygen species (ROS) play critical roles in metabolism and disease, yet a comprehensive analysis of the cellular response to oxidative stress is lacking. To systematically identify regulators of oxidative stress, we conducted genome-wide Cas9/CRISPR and shRNA screens. This revealed a detailed picture of diverse pathways that control oxidative stress response, ranging from the TCA cycle and DNA repair machineries to iron transport, trafficking, and metabolism. Paradoxically, disrupting the pentose phosphate pathway (PPP) at the level of phosphogluconate dehydrogenase (PGD) protects cells against ROS. This dramatically alters metabolites in the PPP, consistent with rewiring of upper glycolysis to promote antioxidant production. In addition, disruption of peroxisomal import unexpectedly increases resistance to oxidative stress by altering the localization of catalase. Together, these studies provide insights into the roles of peroxisomal matrix import and the PPP in redox biology and represent a rich resource for understanding the cellular response to oxidative stress.