Analysis of SARS-CoV-2 variants B.1.617: host tropism, proteolytic activation, cell–cell fusion, and neutralization sensitivity

ABSTRACT

SARS-CoV-2 has caused the COVID-19 pandemic. B.1.617 variants (including Kappa and Delta) have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell–cell fusion after infection of B.1.617 variants were enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.

KEYWORDS:

• SARS-CoV-2 variants
• delta
• B.1.617
• infectivity
• cell–cell fusion
• neutralization

Acknowledgements

We gratefully acknowledge the authors from the originating laboratories and the submitting laboratories where genetic sequence data were generated and shared via GISAID, enabling this research. We thank Prof. Jinghua Yan from Institute of Microbiology, Chinese Academy of Sciences for mAb CB6; Prof. X. Sunney Xie of Peking University for mAbs X593 and X604; Dr. Liangzhi Xie from Sino Biological Company for SCTA01, H02M027, H00S002, H014 and HHV1 mAbs; Dr. Zhiqiang He from Fapon Biotech Inc. for mAb AbG3; Dr. Linqi Zhang of Tsinghua University for mAb A261-262; and Dr. Yuelei Shen of Beijing Biocytogen Inc. for 9G11, 4E5, and 7B8 mAbs. We thank Dr. Jiankai Liu from Shenzhen Kangtai Biological Products Co., Ltd. and Beijing Minhai Biotechnology Co. for providing inactivated vaccine-immunized sera; we thank Prof. Junqiang Li from the Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China and CanSino Biologics Inc. for providing adenovirus vaccine-immunized sera. Y.W., L.Z., J.N., and W.H. conceived, designed, and supervised the experiments; L.Z. and Y.W. wrote the manuscript; Q.L., J.W., Z.C., S.L., H.W., R.D., Z.L., F.J., T.L., L.N., Q.L., J.L., L.Q., and Y.J. performed the experiments for infectivity, host tropism, and neutralization; Y.Y. performed cell fusion experiments; Y.Z. performed proteolysis experiments; Y.S. performed structural analyses; and W.X. provided convalescent sera and clinical data. All authors approved the final manuscript. We thank Ryan Chastain-Gross, Ph.D., from Liwen Bianji (Edanz) (www.liwenbianji.cn), for editing the English text of a draft of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Key Research and Development Program of China [grant number 2021YFC0863300], General Program of the National Natural Science Foundation of China [grant number 82073621, 82172244&32070678], and Bill & Melinda Gates Foundation [Investment ID INV-006379].