A new variant of SARS-CoV-2 B.1.351 lineage (first found in South Africa) has been raising global concern due to its harboring of multiple mutations in the spike that potentially increase transmissibility and yield resistance to neutralizing antibodies. We here tested infectivity and neutralization efficiency of SARS-CoV-2 spike pseudoviruses bearing particular mutations of the receptor-binding domain (RBD) derived either from the Wuhan strains (referred to as D614G or with other sites) or the B.1.351 lineage (referred to as N501Y, K417N, and E484K). The three different pseudoviruses B.1.351 lineage related significantly increased infectivity compared with other mutants that indicated Wuhan strains. Interestingly, K417N and E484K mutations dramatically enhanced cell–cell fusion than N501Y even though their infectivity were similar, suggesting that K417N and E484K mutations harboring SARS-CoV-2 variant might be more transmissible than N501Y mutation containing SARS-CoV-2 variant. We also investigated the efficacy of two different monoclonal antibodies, Casirivimab and Imdevimab that neutralized SARS-CoV-2, against several kinds of pseudoviruses which indicated Wuhan or B.1.351 lineage. Remarkably, Imdevimab effectively neutralized B.1.351 lineage pseudoviruses containing N501Y, K417N, and E484K mutations, while Casirivimab partially affected them. Overall, our results underscore the importance of B.1.351 lineage SARS-CoV-2 in the viral spread and its implication for antibody efficacy.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants of the virus have further exacerbated COVID-19 mortality and infection rates, emphasizing the urgent need for effective preventive strategies. Understanding the viral infection mechanism is crucial for developing therapeutics and vaccines. The entry of SARS-CoV-2 into host cells is a key step in the infection pathway and has been targeted for drug development. Despite numerous reviews of COVID-19 and the virus, there is a lack of comprehensive reviews focusing on the structural aspects of viral entry. In this review, we analyze structural changes in Spike proteins during the entry process, dividing the entry process into prebinding, receptor binding, proteolytic cleavage, and membrane fusion steps. By understanding the atomic-scale details of viral entry, we can better target the entry step for intervention strategies. We also examine the impacts of mutations in Spike proteins, including the Omicron variant, on viral entry. Structural information provides insights into the effects of mutations and can guide the development of therapeutics and vaccines. Finally, we discuss available structure-based approaches for the development of therapeutics and vaccines. Overall, this review provides a detailed analysis of the structural aspects of SARS-CoV-2 viral entry, highlighting its significance in the development of therapeutics and vaccines against COVID-19. Therefore, our review emphasizes the importance of structural information in combating SARS-CoV-2 infection.

Hye-Ra Lee, Un Yung Choi, Sung-Woo Hwang, Stephanie Kim, and Jae U. Jung. Mol. Cells 2016;39:777-82. https://doi.org/10.14348/molcells.2016.0232

Spermidine is essential for cellular growth and acts as a prerequisite of hypusination, a post-translational modification of eukaryotic initiation factor 5A (eIF5A), allowing the translation of polyproline-containing proteins. Here, we show that oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) increases spermidine synthesis and eIF5A hypusination to enhance expression of polyproline-containing latency-associated nuclear antigen (LANA) for viral episomal maintenance. KSHV upregulates intracellular spermidine levels by dysregulating polyamine metabolic pathways in three-dimensional (3D) culture and 2D de novo infection conditions. Increased intracellular spermidine leads to increased eIF5A hypusination, ultimately enhancing LANA expression. In contrast, inhibition of spermidine synthesis or eIF5A hypusination alleviates LANA expression, decreasing viral episomal maintenance and KSHV-infected cell proliferation in vitro and in vivo, which is reversed by spermidine supplement. This demonstrates that KSHV hijacks spermidine synthesis and eIF5A hypusination pathways to enhance LANA expression for viral episomal maintenance, suggesting polyamine metabolism and eIF5A hypusination as therapeutic targets for KSHV-induced tumorigenesis.

The causative factor of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously mutating. Interestingly, identified mutations mainly occur in the spike (S) protein which interacts with the ACE2 receptor and is cleaved via serine protease TMPRSS2. Some mutated strains are becoming dominant in various parts of the globe because of increased transmissibility as well as cell entry efficacy. Remarkably, the neutralizing activity of monoclonal antibodies, convalescent sera, and vaccines against the variants has been reported to be significantly reduced. Therefore, the efficacy of various monoclonal antibodies therapy and vaccines against these variants is becoming a great global concern. We herein summarize the current status of SARS-CoV-2 with gears shifted towards the recent and most common genetic variants in relation to transmission, neutralizing activity, and vaccine efficacy.