The historical view of β-lactams as ineffective antimycobacterials has given way to growing interest in the activity of this class against Mycobacterium tuberculosis (Mtb) in the presence of a β-lactamase inhibitor. However, most antimycobacterial βlactams kill Mtb only or best when the bacilli are replicating. Here, a screen of 1904 β-lactams led to the identification of cephalosporins substituted with a pyrithione moiety at C3′ that are active against Mtb under both replicating and nonreplicating conditions, neither activity requiring a β-lactamase inhibitor. Studies showed that activity against nonreplicating Mtb required the in situ release of the pyrithione, independent of the known class A β-lactamase, BlaC. In contrast, replicating Mtb could be killed both by released pyrithione and by the parent β-lactam. Thus, the antimycobacterial activity of pyrithionecontaining cephalosporins arises from two mechanisms that kill mycobacteria in different metabolic states.

No abstract

Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. As rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of minor virus variants in SARS-COV-2 isolates found in nature or identified from preclinical in vitro and in vivo studies and in the clinic. This study demonstrates that a combination of non-competing antibodies not only provides full coverage against currently circulating variants but also protects against emergence of new such variants and their potential seeding into the population in a clinical setting.

As part of a program to explore the chemistry of β-lactams and their derivatives, we prepared a focused set of benzazetidine, indoline, and indole heterocycles, as well as flexible unconstrained variations of the four-membered heterocyclic compounds. These analogues mimic the threedimensional shape of cephalosporins but are not prone to covalent binding via ring opening. Although these analogues were inactive against the ESKAPE pathogens and Mtb, they represent unique and underexplored chemotypes for future biological screening.

The name of author Sara Palomo Di ́az should be changed to Sara Palomo. The change is reflected in the authorship of this correction.