Defining the risk of SARS-CoV-2 variants on immune protection

DeGrace, Marciela M.; Ghedin, Elodie; Frieman, Matthew B.; Krammer, Florian; Grifoni, Alba; Alisoltani, Arghavan; Alter, Galit; Amara, Rama Rao; Baric, Ralph S.; Barouch, Dan H.; Bloom, Jesse D.; Bloyet, Louis-Marie; Bonenfant, Gaston; Boon, Adrianus C. M.; Boritz, Eli; Bratt, Debbie L.; Bricker, Traci L.; Brown, Liana E.; Buchser, William J.; Carreño, Juan Manuel; Cohen-Lavi, Liel; Darling, Tamarand L.; Davis-Gardner, Meredith E.; Dearlove, Bethany L.; Han, Dongyi; Dittmann, Meike; Doria‐Rose, Nicole A.; Douek, Daniel C.; Drosten, Christian; Edara, Venkata Viswanadh; Ellebedy, Ali H.; Fabrizio, Thomas P.; Ferrari, Guido; Florence, William C.; Fouchier, Ron A. M.; Franks, John; García‐Sastre, Adolfo; Godzik, Adam; Gonzalez‐Reiche, Ana S.; Gordon, Aubree; Haagmans, Bart L.; Halfmann, Peter; Ho, David D.; Holbrook, Michael R.; Huang, Yaoxing; James, Sarah L.; Jaroszewski, Lukasz; Jeevan, Trushar; Johnson, Robert M.; Jones, Terry C.; Joshi, Astha; Kawaoka, Yoshihiro; Kercher, Lisa; Koopmans, Marion; Korber, Bette T.; Koren, Eilay; Koup, Richard A.; LeGresley, Eric B.; Lemieux, Jacob E.; Liebeskind, Mariel J.; Liu, Zhuoming; Livingston, Brandi; Logue, James; Luo, Yang; McDermott, Adrian B.; McElrath, M. Juliana; Meliopoulos, Victoria A.; Menachery, Vineet D.; Montefiori, David C.; Mühlemann, Barbara; Munster, Vincent J.; Munt, Jenny; Nair, Manoj S.; Netzl, Antonia; Niewiadomska, Anna Maria; O’Dell, Sijy; Pekosz, Andrew; Perlman, Stanley; Pontelli, Marjorie Cornejo; Rockx, Barry; Rolland, Morgane; Rothlauf, Paul W.; Sacharen, Sinai; Scheuermann, Richard H.; Schmidt, Stephen D.; Schotsaert, Michael; Schultz‐Cherry, Stacey; Seder, Robert A.; Sedova, Mayya; Sette, Alessandro; Shabman, Reed S.; Shen, Xiaoying; Shi, Pei–Yong; Shukla, Maulik; Simon, Viviana; Stumpf, Spencer; Sullivan, Nancy J.; Thackray, Larissa B.; Theiler, James; Thomas, Paul G.; Trifkovic, Sanja; Türeli, Sina; Turner, Samuel A.; Vakaki, Marianna; Bakel, Harm van; VanBlargan, Laura A.; Vincent, Leah R.; Wallace, Zachary S; Wang, Li; Wang, Maple; Wang, Pengfei; Wang, Wei; Weaver, Scott C.; Webby, Richard J.; Weiss, Carol D.; Wentworth, David E.; Weston, Stuart; Whelan, Sean P. J.; Whitener, Bradley; Wilks, Samuel; Xie, Xuping; Bai, Ying; Yoon, Hyejin; Zhou, Bin; Hertz, Tomer; Smith, Derek J.; Diamond, Michael S.; Post, Diane J.; Suthar, Mehul S.

doi:10.1038/s41586-022-04690-5

Cited by 127 publications

(110 citation statements)

References 129 publications

(146 reference statements)

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“…During the SARS-CoV-2 pandemic, it has become apparent that both humoral and T cell-mediated immune memory are protective and underlie unique contributions to responses against VOCs, thus conversations on whether future vaccinations should include a T cell-specific component are ongoing. Further, initiatives like the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program have been critical for assessing risk of emerging VOCs, their transmission potential, and importantly, the effects these variants have on vaccine-mediated immunity ( DeGrace et al., 2022 ).…”

Section: Outstanding Questionsmentioning

confidence: 99%

Mucosal immune responses to infection and vaccination in the respiratory tract

Mettelman

Allen²,

Thomas³

2022

Immunity

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Section: Outstanding Questionsmentioning

confidence: 99%

Mucosal immune responses to infection and vaccination in the respiratory tract

Mettelman

Allen²,

Thomas³

2022

Immunity

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“…SARS-CoV-2 shows a great capacity of changing genetics and at least 13 variants have been reported so far, with mutations localized in the amino acids present at the N-terminus and the receptor-binding region. The most spread variants have been Alpha, Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), with Delta and Omicron being the most alarming ones [ 3 , 4 ]. Recently, a new variant with the Delta backbone and Omicron spike has been described [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants

et al. 2022

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The novel SARS-CoV-2 variants of concern (VOC) represent a considerable global alarm because their mutations are known to affect transmissibility and cause immune escape. While preventing severe disease and deaths, the available vaccines do not avoid infection; therefore, COVID-19 disease management still requires effective therapies. We have recently reported that the aminothiol cysteamine, a drug already applied to humans, exerts direct antiviral activity against SARS-CoV-2 and has in vitro immunomodulatory effect. To evaluate whether this compound exerts antiviral effects also against SARS-CoV-2 variants, we performed different infected cell-based assays using Wild type, Delta, or Omicron VOC. We found that cysteamine significantly reduces the cytopathic effect induced by SARS-CoV-2 Wild type strain and Delta variant in Vero E6 cells. On the other hand, cysteamine had no effects on the survival of cells infected with the Omicron variant, due to the lack of cytotoxicity on Vero E6 cells, at least when infected at MOI = 0.001 for 72 h. Moreover, cysteamine significantly reduced the production of Wild type, Delta, and Omicron variants as measured by the virus released in the culture media (Vero E6 and Calu-3 cells) and by transmission electron microscopy analysis (Vero E6 cells). Notably, cysteamine is more effective in inhibiting the Omicron rather than Delta or Wild type viruses, with an 80% inhibition of Omicron production compared to 40% of Wild type and Delta variant. Overall, our findings demonstrate that cysteamine exerts direct antiviral actions against SARS-CoV-2 Delta and Omicron variants, in addition to the Wild type virus. Our data further demonstrate that cysteamine is a good candidate as repurposing drug for the treatment of SARS-CoV-2 infection for the present and, likely, the future VOC and, therefore, it would be important to investigate its clinical relevance in randomized clinical trials.

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“…Our group previously developed the Coronavirus3D server (https://coronavirus3d.org/) to analyze the distribution of SARS-CoV-2 mutations in the context of experimental or predicted 3D structures of its proteins [11]. It was later expanded to provide tracking of the dynamics of the emergence of novel variants and mutations as a part of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program [12]. SARS-CoV-2 genomes are downloaded regularly from the GISAID database [13], and the distribution and time patterns of mutations are analyzed to identify fast-growing or track otherwise important mutations.…”

Section: Resultsmentioning

confidence: 99%

Monitoring for SARS-CoV-2 drug resistance mutations in broad viral populations

Sedova

Jaroszewski

Iyer

et al. 2022

Preprint

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The search for drugs against COVID-19 and other diseases caused by coronaviruses focuses on the most conserved and essential proteins, mainly the main (Mpro) and the papain-like (PLpro) proteases and the RNA-dependent RNA polymerase (RdRp). Nirmatrelvir, an inhibitor for Mpro, was recently approved by FDA as a part of a two-drug combination, Paxlovid, and many more drugs are in various stages of development. Multiple candidates for the PLpro inhibitors are being studied, but none have yet progressed to clinical trials. Several repurposed inhibitors of RdRp are already in use. We can expect that once anti-COVID-19 drugs become widely used, resistant variants of SARS-CoV-2 will emerge, and we already see that for the drugs targeting SARS-CoV-2 RdRp. We hypothesize that emergence of such variants can be anticipated by identifying possible escape mutations already present in the existing populations of viruses. Our group previously developed the coronavirus3D server (https://coronavirus3d.org), tracking the evolution of SARS- CoV-2 in the context of the three-dimensional structures of its proteins. Here we introduce dedicated pages tracking the emergence of potential drug resistant mutations to Mpro and PLpro, showing that such mutations are already circulating in the SARS-CoV-2 viral population. With regular updates, the drug resistance tracker provides an easy way to monitor and potentially predict the emergence of drug resistance-conferring mutations in the SARS-CoV-2 virus.

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Defining the risk of SARS-CoV-2 variants on immune protection

Cited by 127 publications

References 129 publications

Mucosal immune responses to infection and vaccination in the respiratory tract

Mucosal immune responses to infection and vaccination in the respiratory tract

Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants

Monitoring for SARS-CoV-2 drug resistance mutations in broad viral populations

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