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The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates.

ABSTRACT: Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking viral receptor angiotensin-converting enzyme 2 (ACE2). The lead drug candidate possessing an Fc tag (Nanosota-1C-Fc) bound to SARS-CoV-2 RBD ~3000 times more tightly than ACE2 did and inhibited SARS-CoV-2 pseudovirus ~160 times more efficiently than ACE2 did. Administered at a single dose, Nanosota-1C-Fc demonstrated preventive and therapeutic efficacy against live SARS-CoV-2 infection in both hamster and mouse models. Unlike conventional antibodies, Nanosota-1C-Fc was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of Nanosota-1C-Fc documented an excellent in vivo stability and a high tissue bioavailability. As effective and inexpensive drug candidates, Nanosota-1 may contribute to the battle against COVID-19.

SUBMITTER: Ye G

PROVIDER: S-EPMC8354634 | biostudies-literature |

REPOSITORIES: biostudies-literature

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SARS-CoV-2 vaccine candidates in rapid development.

Project description:The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading globally. The scientific community is attempting to procure an effective treatment and prevention strategy for COVID-19. A rising number of vaccines for COVID-19 are being developed at an unprecedented speed. Development platforms include traditional inactivated or live attenuated virus vaccines, DNA or RNA vaccines, recombinant viral vector vaccines, and protein or peptide subunit vaccines. There are 23 vaccines in the clinical evaluation stage and at least 140 candidate vaccines in preclinical evaluation. In this review, we describe research regarding basic knowledge on the virus, updates on the animal models, current landscape of vaccines in clinical evaluation and updated research results on vaccine development. Safe and effective COVID-19 vaccines require further investigation.

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Anti-SARS-CoV-1 and -2 nanobody engineering towards avidity-inspired therapeutics.

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Identification of Drug Candidates Rescuing SARS-CoV-2 Infection Induced Dopaminergic Neuron Senescence

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2022-10-01 | GSE156761 | GEO

The Development of a Novel Nanobody Therapeutic for SARS-CoV-2.

Project description:Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a novel series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking out viral receptor ACE2. The lead drug possessing an Fc tag ( Nanosota-1C-Fc ) bound to SARS-CoV-2 RBD with a K d of 15.7picomolar (∼3000 times more tightly than ACE2 did) and inhibited SARS-CoV-2 infection with an ND 50 of 0.16microgram/milliliter (∼6000 times more potently than ACE2 did). Administered at a single dose, Nanosota-1C-Fc demonstrated preventive and therapeutic efficacy in hamsters subjected to SARS-CoV-2 infection. Unlike conventional antibody drugs, Nanosota-1C-Fc was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of Nanosota-1C-F c documented a greater than 10-day in vivo half-life efficacy and high tissue bioavailability. Nanosota-1C-Fc is a potentially effective and realistic solution to the COVID-19 pandemic.Impact statementPotent and low-cost Nanosota-1 drugs block SARS-CoV-2 infections both in vitro and in vivo and act both preventively and therapeutically.

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| S-EPMC7776322 | biostudies-literature

Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies

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| S-SCDT-10_1038-S44318-024-00061-0 | biostudies-other

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| S-EPMC7650805 | biostudies-literature

Computational screening for potential drug candidates against the SARS-CoV-2 main protease.

Project description:Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa M pro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that M pro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 M pro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus.

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| S-EPMC8587465 | biostudies-literature

Synthesis and immunological evaluation of synthetic peptide based anti-SARS-CoV-2 vaccine candidates.

Project description:For prevention of the coronavirus disease 2019 caused by the novel coronavirus SARS-CoV-2, an effective vaccine is critical. Herein, several potential peptide epitopes from the spike protein of SARS-CoV-2 have been synthesized and covalently linked with the cross-reactive material (CRM197). Immunization of mice with the resulting conjugates induced high titers of IgG antibodies against the spike protein. Importantly, the post-immune sera effectively neutralized SARS-CoV-2 pseudovirus, suggesting the epitopes identified are protective, and these conjugates are promising leads for anti-SARS-CoV-2 vaccine development.

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