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… Show more
“…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.…”
Autophagy is a highly conserved dynamic process by which cells deliver their contents to lysosomes for degradation, thus ensuring cell homeostasis. In response to environmental stress, the induction of autophagy is crucial for cell survival. The dysregulation of this degradative process has been implicated in a wide range of pathologies, including lung diseases, representing a relevant potential target with significant clinical outcomes. During lung disease progression and infections, autophagy may exert both protective and harmful effects on cells. In this review, we will explore the implications of autophagy and its selective forms in several lung infections, such as SARS-CoV-2, Respiratory Syncytial Virus (RSV) and Mycobacterium tuberculosis (Mtb) infections, and different lung diseases such as Cystic Fibrosis (CF), Chronic Obstructive Pulmonary Disease (COPD), and Malignant Mesothelioma (MM).
“…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.…”
Autophagy is a highly conserved dynamic process by which cells deliver their contents to lysosomes for degradation, thus ensuring cell homeostasis. In response to environmental stress, the induction of autophagy is crucial for cell survival. The dysregulation of this degradative process has been implicated in a wide range of pathologies, including lung diseases, representing a relevant potential target with significant clinical outcomes. During lung disease progression and infections, autophagy may exert both protective and harmful effects on cells. In this review, we will explore the implications of autophagy and its selective forms in several lung infections, such as SARS-CoV-2, Respiratory Syncytial Virus (RSV) and Mycobacterium tuberculosis (Mtb) infections, and different lung diseases such as Cystic Fibrosis (CF), Chronic Obstructive Pulmonary Disease (COPD), and Malignant Mesothelioma (MM).
“…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 ].…”
Section: Initial Human Adaptation Of Sars-cov-2 Spike Proteinsmentioning
Coronaviruses are a large family of enveloped RNA viruses found in numerous animal species. They are well known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in the human population. In contrast the most recent human hCoV, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we briefly address the significance and perspectives of broad-spectrum therapeutics and vaccines.
“…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 ].…”
Section: Introductionmentioning
confidence: 99%
“…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 ].…”
Section: Introductionmentioning
confidence: 99%
“…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 ].…”
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing an unprecedented pandemic. Although vaccines and antivirals are limiting the spread, SARS-CoV-2 is still under selective pressure in human and animal populations, as demonstrated by the emergence of variants of concern. To better understand the driving forces leading to new subtypes of SARS-CoV-2, we infected an ex vivo cell model of the human upper respiratory tract with Alpha and Omicron BA.1 variants for one month. Although viral RNA was detected during the entire course of the infection, infectious virus production decreased over time. Sequencing analysis did not show any adaptation in the spike protein, suggesting a key role for the adaptive immune response or adaptation to other anatomical sites for the evolution of SARS-CoV-2.
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