The adaptation of SARS-CoV-2 to humans

Abstract

The process of adaptation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans probably had started decades ago, when its ancestor diverged from the bat coronavirus. The adaptive process comprises strategies the virus uses to overcome the respiratory tract defense barriers and replicate and shed in the host cells. These strategies include the impairment of interferon production, hiding immunogenic motifs, avoiding viral RNA detection, manipulating cell autophagy, triggering host cell death, inducing lymphocyte exhaustion and depletion, and finally, mutation and escape from immunity. In addition, SARS-CoV-2 employs strategies to take advantage of host cell resources for its benefits, such as inhibiting the ubiquitin-proteasome system, hijacking mitochondria functions, and usage of enhancing antibodies. It may be anticipated that as the tradeoffs of adaptation progress, the virus destructive burden will gradually subside. Some evidence suggests that SARS-CoV-2 will become part of the human respiratory virome, as had occurred with other coronaviruses, and coevolve with its host.

The Multifaceted Roles of Autophagy in Infectious, Obstructive, and Malignant Airway Diseases

“…All publications available from 2020 agree with the fact that SARS-CoV-2 modifies the autophagic pathway of infected cells, which then creates an escape mechanism against humans’ defenses [ 52 ]. However, how SARS-CoV-2 interferes with autophagy is apparently controversial.…”

Causes and Consequences of Coronavirus Spike Protein Variability

“…Additionally, evolution of SARS-CoV-2 codon usage and the slower-than-expected acquisition of mutations, hinting at a purifying selection during the initial phase of the pandemic, provide insight into the virus’s genomic adaptation strategies [ 85 , 86 ]. Alterations in the RBD of the Spike protein, which increased the affinity for the human ACE2 receptor, proteolytic processing and fusion were suggested to represent adaptive steps critical for efficient human-to-human transmission of SARS-CoV-2 [ 48 , 87 , 88 , 89 ]. Since its emergence, thousands of mutations have been observed, with novel variations continuously emerging as the virus replicates and spreads across the human population [ 90 ].…”

Alpha and Omicron SARS-CoV-2 Adaptation in an Upper Respiratory Tract Model

“…Almost three years after the identification of a novel virus which causes pneumonia, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 600 million people have been infected [ 1 , 2 , 3 ]. Probably originating from bat coronaviruses, SARS-CoV-2 adapted to infect humans [ 1 , 4 , 5 , 6 , 7 ]. The first human infections likely occurred in a Wuhan market in China in December 2019 [ 1 , 8 , 9 , 10 ].…”

“…SARS-CoV-2 variants differ primarily due to mutations in the spike protein, resulting in either increased binding for angiotensin-converting enzyme 2 (ACE-2), the entry receptor, or immune evasion. For instance, the mutation D614G, which became dominant in February 2020 [ 4 , 16 ], confers enhanced binding to ACE-2 and increased transmissibility [ 17 ]. Multiple mutations (e.g., K417N, E484A, and N501Y) were shown to lead to decreased antibody neutralization, as demonstrated by the augmented risk of re-infection with the Omicron variant [ 4 , 14 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

“…For instance, the mutation D614G, which became dominant in February 2020 [ 4 , 16 ], confers enhanced binding to ACE-2 and increased transmissibility [ 17 ]. Multiple mutations (e.g., K417N, E484A, and N501Y) were shown to lead to decreased antibody neutralization, as demonstrated by the augmented risk of re-infection with the Omicron variant [ 4 , 14 , 17 , 18 , 19 , 20 , 21 , 22 ]. However, mutations can also occur in other structural and non-structural proteins, resulting in innate immune evasion and increased viral replication: R203K and G204R in the nucleocapsid enhanced viral fitness [ 23 ] and Δ500−532 in the non-structural protein 1 (NSP1) are associated with decrease in interferon type I [ 24 ].…”