Inhibition of Chikungunya virus early replication by intracellular nanoantibodies targeting nsP2 Epitope Rich Region

Deng，Qiang1,2,3,8; Guo，Zhongmin4,10; Hu，Huan7; Li，Qianlin1,2,3; Zhang，Yingtao5; Wang，Jin11; Liao，Conghui1,2,3,8; Guo，Cheng6; Li，Xiaokang1,2,3,8; Chen，Zeliang1,2,3,8; Lu，Jiahai1,2,3,8,9

2022-12-01

10.1016/j.antiviral.2022.105446

ANTIVIRAL RESEARCH   Impact Factor & Quartile

0166-3542

1872-9096

Chikungunya fever, caused by Chikungunya virus (CHIKV), is an Aedes mosquito-borne disease present worldwide, and millions of CHIKV infections have been reported. Treatment for CHIKV includes supportive care and anti-inflammatory medications, but there are currently no antiviral treatments or vaccines. Nonstructural protein 2 (nsP2) of CHIKV is the most important functional protein mediating virus replication and amplification, making it an ideal antiviral target for CHIKV. In this study, we determined the CHIKV nsP2 Epitope Rich Region, expressed recombinant nsP2 protein, and isolated 5 nsP2-specific nanobodies (Nb-A2, Nb-A9, Nb-D7, Nb-D12 and Nb-E12) from a phage display library comprising variable domains of Camellidae heavy chain-only antibodies (VHH). We subsequently established a stable Nbs-expressing HEK293T cell line to explore antiviral function. The results showed that Nb-A9 inhibited CHIKV replication at the early stage of CHIKV infection in HEK293T cells, and protected cells against CHIKV-induced cytopathic effect (CPE). This is possibly the first report of an Nbs-based strategy against CHIKV nsP2, Nb-A9 has great potential for developing a novel antiviral drug to treat CHIKV infection. The acquisition of antibodies has laid a foundation for further research on the function of CHIKV nsP2 and the development of therapeutic drugs.

Chikungunya virus Mosquito-borne disease Nanobodies Non-structural protein 2 Single-domain antibody VHH

English

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National Key Research and Development Program of China[2018YFE0208000];

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85140653033

Scopus

1.One Health Center of Excellence for Research and Training,School of Public Health,Sun Yat-sen University,Guangzhou,510080,China
2.NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products,Guangzhou,510080,China
3.Key Laboratory of Tropical Diseases Control,Sun Yat-Sen University,Ministry of Education,Guangzhou,510080,China
4.Laboratory Animal Center,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,510080,China
5.Guangdong Provincial Center for Disease Control and Prevention,Guangzhou,510080,China
6.Center for Infection and Immunity,Mailman School of Public Health,Columbia University,New York,United States
7.Department of Biomedical Sciences,City University of Hong Kong,Hong Kong
8.Research Institute of Sun Yat-Sen University in Shenzhen,Shenzhen,518057,China
9.Hainan Key Novel Thinktank “Hainan Medical University ‘One Health’ Research Center”,Haikou,571199,China
10.Experimental Animal Center,Sun Yat-sen University,Guangzhou,Guangdong Province,China
11.Department of Pulmonary Medicine,National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,China

Deng，Qiang,Guo，Zhongmin,Hu，Huan,et al. Inhibition of Chikungunya virus early replication by intracellular nanoantibodies targeting nsP2 Epitope Rich Region[J]. ANTIVIRAL RESEARCH,2022,208.

Deng，Qiang.,Guo，Zhongmin.,Hu，Huan.,Li，Qianlin.,Zhang，Yingtao.,...&Lu，Jiahai.(2022).Inhibition of Chikungunya virus early replication by intracellular nanoantibodies targeting nsP2 Epitope Rich Region.ANTIVIRAL RESEARCH,208.

Deng，Qiang,et al."Inhibition of Chikungunya virus early replication by intracellular nanoantibodies targeting nsP2 Epitope Rich Region".ANTIVIRAL RESEARCH 208(2022).