Highlights d A SARS-CoV-2 variant with Spike G614 has replaced D614 as the dominant pandemic form d The consistent increase of G614 at regional levels may indicate a fitness advantage d G614 is associated with lower RT PCR Cts, suggestive of higher viral loads in patients d The G614 variant grows to higher titers as pseudotyped virions

Antibody levels predict vaccine efficacy Symptomatic COVID-19 infection can be prevented by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. A “correlate of protection” is a molecular biomarker to measure how much immunity is needed to fight infection and is key for successful global immunization programs. Gilbert et al . determined that antibodies are the correlate of protection in vaccinated individuals enrolled in the Moderna COVE phase 3 clinical trial (see the Perspective by Openshaw). By measuring binding and neutralizing antibodies against the viral spike protein, the authors found that the levels of both antibodies correlated with the degree of vaccine efficacy. The higher the antibody level, the greater the protection afforded by the messenger RNA (mRNA) vaccine. Antibody levels that predict mRNA vaccine efficacy can therefore be used to guide vaccine regimen modifications and support regulatory approvals for a broader spectrum of the population. —PNK

To define the role of the huma immuaodeciency virus type 1 (HIV-1) envelope proteins in virus infection, a series ofpeptides were synthesized based on various regions ofthe HIV-1 transmembrane protein gp4l. One of these peptides, DP-178, corresponding to a region predictive of a-helical secondary structure (residues 643-678 ofthe H1V-1LA isolate),.has been identified as a potent antivia agent. This peptide consistently blocked 100% of virus-mediated cell-cell fusion at <5 ng/ml (I(C2o 1.5 ng/ml) and gave an -10 times reduction in infectious titer of cel-free virus at =80 ng/ml. The inhibitory activity was observed at peptide concentrations _104 to 105 times lower than those at which cytotoxicity and cytostasis were detected. Peptidemediated inhibition is H1V-1 specific in that =102 to 10 times more peptide was required for inhibition of a human immunodeficiency virus type 2 isolate. Further experiments showed that DP-178 exhibited antiviral activity against both prototypic and primary IHV-1 isolates. As shown by PCR analysis of newly synthesized proviral DNA, DP-178 blocks an early step in the virus life cycle prior to reverse transcription. Finally, we discuss possible mechanisms by which DP-178 may exert its inhibitory activity.

A peptide designated DP-107 was synthesized containing amino acid residues 558-595 of the envelope glycoprotein gpl60 of human immunodeficiency virus type 1 strain LAI (HIV-Lhm). Algorithms for secondary structure have predicted that this region of the envelope tansmembrane protein should form an extended a-helix. Consistent with this prediction, analysis by circular dichroism (CD) indicated that, under physiological conditions, DP-107 is =85% helical. The high degree of stable secondary structure in a synthetic peptide of this size suggests self-association typical of a coiled coil or leucine zipper. In biological assays, the peptide efficiently blocked virus-mediated cell-cell fusion processes as well as infection of peripheral blood mononuclear celis by both prototypic and primary isolates of HIV-1. A single amino add substitution in the peptide greatly destabilized its solution structure as measured by CD and abrogated its antiviral activity. An analogue containing a terminal cysteine was oxidized to form a dimer, and this modification lowered the dose required for antiviral effect from S to about 1 pg/mi. These results suggest that both oligomerization and ordered structure are necessary for biological activity. They provide inights also into the role of this region in H1V infection and the potential for development of a new class of antiviral agents.Of the anti-human immunodeficiency virus (HIV) treatment strategies tested to date, none is curative and only certain inhibitors of the viral reverse transcriptase (RT) have demonstrated clinical benefit (1). As a result, the search for new, more efficacious drugs and/or other sites on the virus against which to target antiviral therapy continues at an urgent pace. In this report we describe a synthetic peptide which appears to possess potent antiviral activity in vitro and may represent a lead to a new class of antiretroviral agents. The peptide sequence is based on a highly conserved region in the transmembrane (TM) protein which was predicted by Gallaher et al. (2) to form an extended amphipathic a-helix with structural analogues in the TM proteins of several fusogenic viruses, such as influenza virus and other retroviruses. The function of the site is not known but may be related to multimerization of the envelope glycoprotein.Our interest in the TM protein region described above was heightened by reports that its primary sequence is strongly predictive of an extended amphipathic a-helix (2) and contains a "leucine zipper" repeat (3). O'Shea et al. (4) have demonstrated that the latter type of structural motif can be modeled using synthetic peptides. We reasoned that if this region of gp4l exhibited a similar type of structure (specifically, subunit oligomerization to form coiled coils) we might successfully model this process with synthetic peptides. If so, then these models could be used to study the relationship of secondary structure to several important aspects of viral replication, including multimerization and the effect of mutations within ...