A Novel Neutralizing Antibody Targeting Receptor Binding Domain of SARS-CoV-2

Lee, Sang Yup; Kim, Cheol-Min; Ryu, Dong-Kyun; Kim, Young Il; Seo, Ji-Min; kim, Yeon-Gil; Jeong, Jin Ho; Kim, Min‐Soo; Kim, Jong-In; Kim, Pankyeom; Bae, Jin Soo; Shim, Eun Yeong; Lee, Min Seob; Kim, Man Su; Noh, Hanmi; Park, Geun-Soo; Park, Jae Sang; Son, Dain; An, Yongjin; Lee, Jeong No; Kwon, Kisung; Lee, Joo-Yeon; Lee, Hansaem; Yang, Jeong‐Sun; Kim, Kyung-Chang; Kim, Sung Soon; Woo, Hye‐Min; Kim, Jun Won; Park, Man‐Seong; Yu, Kwang-Min; Kim, Se‐Mi; Kim, Eunha; Park, Su‐Jin; Jeong, Seong Tae; Yu, Chi Ho; Song, Young-Suk; Gu, Se Hun; Oh, Hanseul; Koo, Bon‐Sang; Hong, Jung Joo; Ryu, Choong-Min; Park, Wan Beom; Oh, Myoung‐don; Choi, Young Ki

doi:10.21203/rs.3.rs-59639/v1

Cited by 4 publications

(2 citation statements)

References 32 publications

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“…Asterisks mark amino acid residues interacting with ACE2, and hash signs indicate amino acid residues interacting with at least one of 13 neutralizing antibodies with a known three-dimensional structure (in accordance with Fig. 2 from Lee et al [ 11 ]). Interaction criterion – the distance between residues is not more than 4.5 Å.…”

Section: Resultsmentioning

confidence: 53%

Development of a Platform for Producing Recombinant Protein Components of Epitope Vaccines for the Prevention of COVID-19

Karyagina

Gromov

Грунина

et al. 2021

Biochemistry Moscow

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A new platform for creating anti-coronavirus epitope vaccines has been developed. Two loop-like epitopes with lengths of 22 and 42 amino acid residues were selected from the receptor-binding motif of the Spike protein from the SARS‑CoV‑2 virus that participate in a large number of protein-protein interactions in the complexes with ACE2 and neutralizing antibodies. Two types of hybrid proteins, including one of the two selected epitopes, were constructed. To fix conformation of the selected epitopes, an approach using protein scaffolds was used. The homologue of Rop protein from the Escherichia coli ColE1 plasmid containing helix-turn-helix motif was used as an epitope scaffold for the convergence of C- and N-termini of the loop-like epitopes. Loop epitopes were inserted into the turn region. The conformation was additionally fixed by a disulfide bond formed between the cysteine residues present within the epitopes. For the purpose of multimerization, either aldolase from Thermotoga maritima , which forms a trimer in solution, or alpha-helical trimerizer of the Spike protein from SARS‑CoV‑2, was attached to the epitopes incorporated into the Rop-like protein. To enable purification on the heparin-containing sorbents, a short fragment from the heparin-binding hemagglutinin of Mycobacterium tuberculosis was inserted at the C-terminus of the hybrid proteins. All the obtained proteins demonstrated high level of immunogenicity after triplicate parenteral administration to mice. Sera from the mice immunized with both aldolase-based hybrid proteins and the Spike protein SARS‑CoV‑2 trimerizer-based protein with a longer epitope interacted with both the inactivated SARS‑CoV‑2 virus and the Spike protein receptor-binding domain at high titers. Supplementary information The online version contains supplementary material available at 10.1134/S0006297921100096.

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Section: Resultsmentioning

confidence: 53%

Development of a Platform for Producing Recombinant Protein Components of Epitope Vaccines for the Prevention of COVID-19

Karyagina

Gromov

Грунина

et al. 2021

Biochemistry Moscow

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“…For example, the S protein blockers casirivimab/imdevimab, also known as REGN10933/REGN10987 64 and Bamlanivimab (LY-CoV555) 65 which have both been issued with emergency use authorisation by the FDA, for use in non-hospitalised patients not requiring oxygen. Also under investigation in animal models, is CT-P59, which targets the receptor binding protein of SARS-CoV2 66 . Casirivimab/imdevimab showed significant reductions in virus levels and were associated with significantly fewer medical visits 64 .…”

Section: The Way Forwardmentioning

confidence: 99%

COVID-19: A need for new rather than repurposed antiviral drugs

Kovacs

Davis

Cannon

et al. 2021

Preprint

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Background: SARS-CoV-2 infection, the causative agent of COVID-19, has resulted in over 2,500,000 deaths to date. Although vaccines are becoming available, treatment options remain limited. Repurposing of compounds could reduce the time, cost, and risks associated with the development of new drugs and has been the focus of many clinical studies. Here, we summarise available evidence on 29 FDA-approved compounds, from in vitro results to clinical trials, focussing on remdesivir, galidesivir and favipiravir, and test 29 antiviral compounds activity in vitro. Methods: A comprehensive search strategy was used to retrieve trials and publications related to antiviral compounds with potential efficacy to treat coronaviruses. These data were used to prioritise testing of a panel of antiviral drugs in vitro against patient isolates of SARS-CoV-2. An in vitro screen was carried out to determine the activity of 29 FDA-approved compounds. Results: 625 clinical trials investigated 16 repurposed antiviral candidate compounds for the treatment of COVID-19. In vitro studies identified ten drug candidates with demonstrable anti-SARS-CoV-2 activity, including favipiravir, remdesivir, and galidesivir. To validate these findings, a drug screen was conducted using two cell lines and wildtype isolates of SARS-CoV-2 isolated from patients in the UK. While eight drugs with anti-SARS-CoV-2 activity were identified in vitro, activity in clinical trials has, as yet failed to demonstrate a strong effect on mortality. Conclusions: So far, no repurposed antiviral has shown a strong effect on mortality in clinical studies. The urgent need for novel antivirals in this pandemic is clear, despite the costs and time associated with their development.

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