Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease.
Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease.
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DOI：
10.1016/j.chom.2021.06.008
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发表时间：
2021-07-14
影响因子：
30.3
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
Case JB;Chen RE;Cao L;Ying B;Winkler ES;Johnson M;Goreshnik I;Pham MN;Shrihari S;Kafai NM;Bailey AL;Xie X;Shi PY;Ravichandran R;Carter L;Stewart L;Baker D;Diamond MS
Despite the introduction of public health measures and spike protein-based vaccines to mitigate the COVID-19 pandemic, SARS-CoV-2 infections and deaths continue to have a global impact. Previously, we used a structural design approach to develop picomolar range miniproteins targeting the SARS-CoV-2 spike receptor-binding domain. Here, we investigated the capacity of modified versions of one lead miniprotein, LCB1, to protect against SARS-CoV-2-mediated lung disease in mice. Systemic administration of LCB1-Fc reduced viral burden, diminished immune cell infiltration and inflammation, and completely prevented lung disease and pathology. A single intranasal dose of LCB1v1.3 reduced SARS-CoV-2 infection in the lung when given as many as 5 days before or 2 days after virus inoculation. Importantly, LCB1v1.3 protected in vivo against a historical strain (WA1/2020), an emerging B.1.1.7 strain, and a strain encoding key E484K and N501Y spike protein substitutions. These data support development of LCB1v1.3 for prevention or treatment of SARS-CoV-2 infection. Case et al. show that de novo-designed SARS-CoV-2 RBD-specific miniproteins administered as prophylaxis or therapy protect mice against SARS-CoV-2-mediated disease, inflammation, and pathology. Injected or intranasal administration of miniproteins showed efficacy when given any time over an 8-day treatment window.
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DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
影响因子：
64.8
作者：
Chevalier A;Silva DA;Rocklin GJ;Hicks DR;Vergara R;Murapa P;Bernard SM;Zhang L;Lam KH;Yao G;Bahl CD;Miyashita SI;Goreshnik I;Fuller JT;Koday MT;Jenkins CM;Colvin T;Carter L;Bohn A;Bryan CM;Fernández-Velasco DA;Stewart L;Dong M;Huang X;Jin R;Wilson IA;Fuller DH;Baker D
通讯作者：
Baker D
影响因子：
32.4
作者：
Hoagland DA;Møller R;Uhl SA;Oishi K;Frere J;Golynker I;Horiuchi S;Panis M;Blanco-Melo D;Sachs D;Arkun K;Lim JK;tenOever BR
通讯作者：
tenOever BR
影响因子：
3.7
作者：
Case, James Brett;Bailey, Adam L.;Diamond, Michael S.
通讯作者：
Diamond, Michael S.
DOI：
10.2807/1560-7917.es.2020.26.1.2002106
发表时间：
2021-01
期刊：
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin
影响因子：
--
作者：
Leung K;Shum MH;Leung GM;Lam TT;Wu JT
通讯作者：
Wu JT