Unknown

Dataset Information

0

Structural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections.


ABSTRACT: Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV's "Achilles heel", defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies.

SUBMITTER: Sevvana M 

PROVIDER: S-EPMC7760643 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications


Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the viru  ...[more]

Similar Datasets

| S-EPMC4983199 | biostudies-literature
| S-EPMC8308650 | biostudies-literature
| S-EPMC5382833 | biostudies-literature
| S-EPMC6007842 | biostudies-literature
| S-EPMC3050594 | biostudies-literature
| S-EPMC9742325 | biostudies-literature
| S-EPMC3202596 | biostudies-literature
| S-EPMC3792640 | biostudies-literature
| S-EPMC4980333 | biostudies-literature
| S-EPMC7095628 | biostudies-literature