SARS-CoV-2 variants show a gradual declining pathogenicity and pro-inflammatory cytokine spur, an increasing antigenic and antiinflammatory cytokine induction, and rising structural protein instability

Barh, Debmalya; Tiwari, Sandeep; Gomes, Lucas Gabriel Rodrigues; Pinto, Cecília Horta Ramalho; Andrade, Bruno Silva; Ahmad, Shaban; Aljabali, Alaa A. A.; Alzahrani, Khalid J.; Banjer, Hamsa Jameel; Hassan, Sk. Sarif; Tambuwala, Murtaza M.; Redwan, Elrashdy M.; Raza, Khalid; Azevedo, Vasco; Lundström, Kenneth; Uversky, Vladimir N.

doi:10.1101/2022.02.15.480592

Cited by 10 publications

(14 citation statements)

References 53 publications

(71 reference statements)

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“…An in vivo mouse study showed a differential induction of cytokines by the delta and omicron variants in comparison to an early G614 isolate (62); and similarly, an in vivo study in hamsters showed reduced levels of a range of cytokines in omicron infected compared to delta infected animals (63), suggesting that the variants are indeed inducing different cytokine levels in vivo. One study has analyzed various SARS-CoV-2 proteins for the presence of cytokine-inducing peptides and found significant contribution of proteins other than spike to the cytokine response, which was found to be slightly reduced for omicron in comparison to Wuhan Hu-1, gamma (B.1.1.28.1) and delta derived proteins (64). Furthermore it has been shown in in vitro studies that omicron is more susceptible to inhibition by type I interferons and induces higher levels of type I interferons than delta (65,66), which may also play a role in the development of fever.…”

Section: Discussionmentioning

confidence: 99%

Changes in Symptoms Experienced by SARS-CoV-2-Infected Individuals – From the First Wave to the Omicron Variant

Schulze¹,

Bayer²

2022

Front. Virol.

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic and public health crisis since the beginning of 2020. First recognized for the induction of severe disease, the virus also causes asymptomatic infections or infections with mild symptoms that can resemble common colds. To provide better understanding of these mild SARS-CoV-2 infections and to monitor the development of symptoms over time, we performed a detailed analysis of self-reported symptoms of SARS-CoV-2 positive and SARS-CoV-2 negative individuals. In an online-based survey, a total of 2117 individuals provided information on symptoms associated with an acute respiratory infection, 1925 of the participants had tested positive for SARS-CoV-2 infection, and 192 had tested negative. The symptoms reported most frequently during the early phases of the pandemic by SARS-CoV-2 infected individuals were tiredness, headache, impairment of smell or taste and dry cough. With the spread of the alpha and delta variants, the frequency of nose symptoms such as blocked or runny nose and sneezing increased to being reported by almost 60% of infected individuals. Interestingly, the spread of the omicron variant brought a sharp decrease in the incidence of impaired sense of smell or taste, which was reported by only 24% in this phase of the pandemic. The constellation of symptoms should be monitored closely in the months ahead, since future SARS-CoV-2 variants are likely to bring about more changes.

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Section: Discussionmentioning

confidence: 99%

Changes in Symptoms Experienced by SARS-CoV-2-Infected Individuals – From the First Wave to the Omicron Variant

Schulze¹,

Bayer²

2022

Front. Virol.

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“…Consistent with this observation, a recent study reveals that decreased disease severity by Omicron variant may due to increased anti-inflammatory IFN-γ and decreased pro-inflammatory cytokine responses (IL-6) [36]. In the future, it would be interesting to assess and compare expression of such cytokines in tissues, particularly targeting the most severely affected tissues in the upper and lower respiratory tract of infected cats.…”

Section: Discussionmentioning

confidence: 62%

The Omicron variant BA.1.1 presents a lower pathogenicity than B.1 D614G and Delta variants in a feline model of SARS-CoV-2 infection

Martins

Nascimento

Nooruzzaman

et al. 2022

Preprint

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Omicron (B.1.1.529) is the most recent SARS-CoV-2 variant of concern (VOC), which emerged in late 2021 and rapidly achieved global predominance in early 2022. In this study, we compared the infection dynamics, tissue tropism and pathogenesis and pathogenicity of SARS-CoV-2 D614G (B.1), Delta (B.1.617.2) and Omicron BA.1.1 sublineage (B.1.1.529) variants in a highly susceptible feline model of infection. While D614G- and Delta-inoculated cats became lethargic, and showed increased body temperatures between days 1 and 3 post-infection (pi), Omicron-inoculated cats remained subclinical and, similar to control animals, gained weight throughout the 14-day experimental period. Intranasal inoculation of cats with D614G- and the Delta variants resulted in high infectious virus shedding in nasal secretions (up to 6.3 log10 TCID50.ml-1), whereas strikingly lower level of viruses shedding (<3.1 log10 TCID50.ml-1) was observed in Omicron-inoculated animals. In addition, tissue distribution of the Omicron variant was markedly reduced in comparison to the D614G and Delta variants, as evidenced by in situ viral RNA detection, in situ immunofluorescence, and quantification of viral loads in tissues on days 3, 5, and 14 pi. Nasal turbinate, trachea, and lung were the main - but not the only - sites of replication for all three viral variants. However, only scarce virus staining and lower viral titers suggest lower levels of viral replication in tissues from Omicron-infected animals. Notably, while D614G- and Delta-inoculated cats had severe pneumonia, histologic examination of the lungs from Omicron-infected cats revealed mild to modest inflammation. Together, these results demonstrate that the Omicron variant BA.1.1 is less pathogenic than D614G and Delta variants in a highly susceptible feline model.

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“…5 Those who develop symptoms noticeable enough to be classed as patients develop mild-to-moderate symptoms (up to mild pneumonia). [5][6][7][8] In contrast, few develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging), and few suffer acute symptoms (respiratory failure, shock, or multiorgan dysfunction). Apart from this, many testing methods have been developed to diagnose the condition.…”

Section: Introductionmentioning

confidence: 99%

“…As the cases and new variants evolve daily, fear continues, and there is still no medication on the market. 6,7 Most of the previous studies were from single target and multiple drug backgrounds. 18,19 Nevertheless, in this study, we are reporting N-{2-[(2S)-2-Amino-3-methylbutoxy]-6-pro-pylbenzoyl}-L-phenylalanyl-L-serine (Butoxypheser) 20 as the multitargeted inhibitor that has been identified after comprehensive pipeline-based research.…”

Section: Introductionmentioning

confidence: 99%

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Multitargeted Molecular Dynamic Understanding of Butoxypheser Against SARS-CoV-2: An in Silico Study

Ahmad

Bano

Qazi

et al. 2022

Natural Product Communications

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was initially reported in the Wuhan province of China, spread throughout the world, and caused massive destruction in the form of a global pandemic that started back in 2020. SARS-CoV-2 is an RNA virus with various proteins like main protease, spike protein, NSP15 endoribonuclease, RNA-dependent RNA polymerase, and papain-like protease targeted to screen and find the novel drug candidate that can potentially work against the virus. Previous studies have reported multiple drugs after screening and validation against a single target and reported multiple medications. Nevertheless, many drugs are being used to date but do not have enough potential to work against SARS-CoV-2 and curb the spread and death rate. In this study, with the hypothesis of 1 drug and multiple targets, we have taken 5 main target proteins and screened the Asinex's complete BioDesign library (1,70,269 compounds) and identified N-{2-[(2S)-2-Amino-3-methylbutoxy]-6-propylbenzoyl}-L-phenylalanyl-L-serine (Butoxypheser) as multitarget inhibitor against SARS-CoV-2. Also, Butoxypheser has shown excellent docking scores, hydrogen bonding, and other bonding configurations like van der Waals force and water bridges. The stability and interaction pattern of the compound was validated with structural interaction fingerprints (SIFts) and molecular dynamics (MD) simulation. The Butoxypheser has performed flawlessly throughout the study, and the same results were used to compare the compound's activity against multiple targets. After a thorough theoretical comparative analysis, Butoxypheser can be treated as a multitargeted inhibitor candidate against SARS-CoV-2. Further, this study needs to be validated experimentally before human use.

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SARS-CoV-2 variants show a gradual declining pathogenicity and pro-inflammatory cytokine spur, an increasing antigenic and antiinflammatory cytokine induction, and rising structural protein instability

Cited by 10 publications

References 53 publications

Changes in Symptoms Experienced by SARS-CoV-2-Infected Individuals – From the First Wave to the Omicron Variant

Changes in Symptoms Experienced by SARS-CoV-2-Infected Individuals – From the First Wave to the Omicron Variant

The Omicron variant BA.1.1 presents a lower pathogenicity than B.1 D614G and Delta variants in a feline model of SARS-CoV-2 infection

Multitargeted Molecular Dynamic Understanding of Butoxypheser Against SARS-CoV-2: An in Silico Study

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