Predicting the mutational drivers of future SARS-CoV-2 variants of concern
Michael M. Maher,Sh.Mavlonov +1 more
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TLDR
In this paper , the predictive value of features comprising epidemiology, evolution, immunology, and neural network-based protein sequence modeling was used to identify primary biological drivers of SARS-CoV-2 intrapandemic evolution.Abstract:
SARS-CoV-2 evolution threatens vaccine- and natural infection–derived immunity and the efficacy of therapeutic antibodies. To improve public health preparedness, we sought to predict which existing amino acid mutations in SARS-CoV-2 might contribute to future variants of concern. We tested the predictive value of features comprising epidemiology, evolution, immunology, and neural network–based protein sequence modeling and identified primary biological drivers of SARS-CoV-2 intrapandemic evolution. We found evidence that ACE2-mediated transmissibility and resistance to population-level host immunity has waxed and waned as a primary driver of SARS-CoV-2 evolution over time. We retroactively identified with high accuracy (area under the receiver operator characteristic curve = 0.92 to 0.97) mutations that will spread, at up to 4 months in advance, across different phases of the pandemic. The behavior of the model was consistent with a plausible causal structure where epidemiological covariates combine the effects of diverse and shifting drivers of viral fitness. We applied our model to forecast mutations that will spread in the future and characterize how these mutations affect the binding of therapeutic antibodies. These findings demonstrate that it is possible to forecast the driver mutations that could appear in emerging SARS-CoV-2 variants of concern. We validated this result against Omicron, showing elevated predictive scores for its component mutations before emergence and rapid score increase across daily forecasts during emergence. This modeling approach may be applied to any rapidly evolving pathogens with sufficiently dense genomic surveillance data, such as influenza, and unknown future pandemic viruses. read more
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The Evolution and Biology of SARS-CoV-2 Variants
TL;DR: The most important adaptation of the bat coronavirus progenitor of both SARS-CoV-1 and SARS CoV-2 for human infection (and other mammals) is the use of the angiotensin-converting enzyme 2 (ACE2) receptor as mentioned in this paper .
Journal ArticleDOI
Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains
Tyler N. Starr,Allison J. Greaney,Cameron Stewart,Alexandra C. Walls,William W. Hannon,David Veesler,Jesse D. Bloom +6 more
TL;DR: SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition, and these mutations shape the future evolutionary potential of the virus through the phenomenon of epistasis.
Journal ArticleDOI
Evolutionary velocity with protein language models predicts evolutionary dynamics of diverse proteins.
TL;DR: The authors used a protein language model to predict the local evolution within protein families and recover a dynamic "vector field" of protein evolution that they call evolutionary velocity (evo-velocity).
Journal ArticleDOI
The evolution of SARS-CoV-2
Peter V. Markov,Mahan Ghafari,Martin Beer,Katrina A. Lythgoe,Peter Simmonds,Nikolaos I. Stilianakis,Aris Katzourakis +6 more
TL;DR: In this paper , the authors explored the mechanisms that generate genetic variation in SARS-CoV-2, underlying the within-host and population-level processes that underpin these events, and examined the selective forces that likely drove the evolution of higher transmissibility and, in some cases, higher severity during the first year of the pandemic and the role of antigenic evolution during the second and third years.
Journal ArticleDOI
An early warning system for emerging SARS-CoV-2 variants
Lorenzo Subissi,Anne von Gottberg,Lipi Thukral,Nathalie Worp,Bas B. Oude Munnink,Surabhi Rathore,Laith J. Abu-Raddad,Ximena Aguilera,E. A. Alm,Brett N. Archer,Homa Attar Cohen,Amal Barakat,Wendy S. Barclay,Jinal N. Bhiman,Leon Caly,Meera Chand,Mark Chen,Ann Cullinane,Tulio de Oliveira,Christian Drosten,Julian Druce,P Effler,Ihab El Masry,Adama Faye,Simani Gaseitsiwe,Elodie Ghedin,Rebecca L. Grant,Bart L. Haagmans,Belinda L. Herring,Shilpa S Iyer,Zyleen Kassamali,Manish Kakkar,Rebecca Kondor,Juliana Alves Leite,Yee Sin Leo,Gabriel M. Leung,Marco Marklewitz,Sikhulile Moyo,Jairo Mendez-Rico,Nada M. Melhem,Vincent J. Munster,Karen Martun Nahapetyan,Djin-Ye Oh,Boris I. Pavlin,Thomas P. Peacock,Malik Peiris,Zhibin Peng,Leo L. M. Poon,Andrew Rambaut,Jilian A. Sacks,Yinzhong Shen,Marilda M. Siqueira,Sofonias K. Tessema,Erik M. Volz,Volker Thiel,S. Van Der Werf,Sylvie Briand,Mark D. Perkins,Maria D. Van Kerkhove,Marion Koopmans,Anurag Agrawal +60 more
TL;DR: In this paper , global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic.
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Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding.
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TL;DR: It is found that a substantial number of mutations to the RBD are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses.