Dataset Information

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

ABSTRACT: The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.

SUBMITTER: Ryu DK

PROVIDER: S-EPMC8436435 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

Ryu Dong-Kyun DK Kang Bobin B Noh Hanmi H Woo Sun-Je SJ Lee Min-Ho MH Nuijten Patricia M PM Kim Jong-In JI Seo Ji-Min JM Kim Cheolmin C Kim Minsoo M Yang Eunji E Lim Gippeum G Kim Seong-Gyu SG Eo Su-Kyeong SK Choi Jung-Ah JA Song Manki M Oh Sang-Seok SS Chung Hyo-Young HY Tijsma Aloys Sl AS van Baalen Carel A CA Kwon Ki-Sung KS Lee Soo-Young SY

Biochemical and biophysical research communications 20210913

The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variant ...[more]

PMID: 34547629

Similar Datasets

Project description:Monoclonal antibodies (MAbs) targeting the Spike glycoprotein of SARS-CoV-2 is a key strategy to prevent severe COVID-19. Here, the efficacy of two monoclonal antibody bitherapies against SARS-CoV-2 was assessed on 92 patients at high risk of severe COVID-19 between March and October 2021 (Bichat-Claude Bernard Hospital, Paris, France). Nine patients died despite appropriate management. From 14 days following treatment initiation, we observed a slower viral load decay for patients treated with the bitherapy Bamlanivimab/Etsevimab compared to the Casirivimab/Imdevimab association therapy (P = 0.045). The emergence of several mutations on the Spike protein known to diminish antiviral efficacy was observed from 1 to 3 weeks after infusion. The Q493R mutation was frequently selected, located in a region of joint structural overlap by Bamlanivimab/Etsevimab antibodies. Despite that this study was done on former SARS-CoV-2 variants (Alpha and Delta), the results provide new insights into resistance mechanisms in SARS-CoV-2 antibodies neutralization escape and should be considered for current and novel variants. IMPORTANCE Monoclonal antibody bitherapies (MAbs) are commonly prescribed to treat severe SARS-CoV-2-positive patients, and the rapid growth of resistance mutation emergence is alarming globally. To explore this issue, we conducted both clinical and genomic analyses of SARS-CoV-2 in a series of patients treated in 2021. We first noticed that the two dual therapies prescribed during the study had different kinetics of viral load decay. Rapidly after initiation of the treatments, resistance mutations emerged in the interface between the MAbs and the target Spike glycoprotein, demonstrating the importance to continuously screen the viral genome during treatment course. Taken together, the results highlight that viral mutations may emerge under selective pressure, conferring a putative competitive advantage, and could rapidly spread, as observed for the Omicron variant.

Project description:BackgroundCOVID-19 and Middle East Respiratory Syndrome are two pandemic respiratory diseases caused by coronavirus species. The novel disease COVID-19 caused by SARS-CoV-2 was first reported in Wuhan, Hubei Province, China, in December 2019, and became a pandemic within 2-3 months, affecting social and economic platforms worldwide. Despite the rapid development of vaccines, there have been obstacles to their distribution, including a lack of fundamental resources, poor immunization, and manual vaccine replication. Several variants of the original Wuhan strain have emerged in the last 3 years, which can pose a further challenge for control and vaccine development.ObjectiveThe aim of this study was to comprehensively analyze mutations in SARS-CoV-2 variants of concern (VoCs) using a bioinformatics approach toward identifying novel mutations that may be helpful in developing new vaccines by targeting these sites.MethodsReference sequences of the SARS-CoV-2 spike (YP_009724390) and nucleocapsid (YP_009724397) proteins were compared to retrieved sequences of isolates of four VoCs from 14 countries for mutational and evolutionary analyses. Multiple sequence alignment was performed and phylogenetic trees were constructed by the neighbor-joining method with 1000 bootstrap replicates using MEGA (version 6). Mutations in amino acid sequences were analyzed using the MultAlin online tool (version 5.4.1).ResultsAmong the four VoCs, a total of 143 nonsynonymous mutations and 8 deletions were identified in the spike and nucleocapsid proteins. Multiple sequence alignment and amino acid substitution analysis revealed new mutations, including G72W, M2101I, L139F, 209-211 deletion, G212S, P199L, P67S, I292T, and substitutions with unknown amino acid replacement, reported in Egypt (MW533289), the United Kingdom (MT906649), and other regions. The variants B.1.1.7 (Alpha variant) and B.1.617.2 (Delta variant), characterized by higher transmissibility and lethality, harbored the amino acid substitutions D614G, R203K, and G204R with higher prevalence rates in most sequences. Phylogenetic analysis among the novel SARS-CoV-2 variant proteins and some previously reported β-coronavirus proteins indicated that either the evolutionary clade was weakly supported or not supported at all by the β-coronavirus species.ConclusionsThis study could contribute toward gaining a better understanding of the basic nature of SARS-CoV-2 and its four major variants. The numerous novel mutations detected could also provide a better understanding of VoCs and help in identifying suitable mutations for vaccine targets. Moreover, these data offer evidence for new types of mutations in VoCs, which will provide insight into the epidemiology of SARS-CoV-2.

Dataset Information

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

Publications

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets