Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus.
Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus.
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DOI：
10.3390/v13020234
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发表时间：
2021-02-03
期刊：
影响因子：
--
通讯作者：
Chang KC
中科院分区：
文献类型：
--
作者：
Al-Beltagi S;Preda CA;Goulding LV;James J;Pu J;Skinner P;Jiang Z;Wang BL;Yang J;Banyard AC;Mellits KH;Gershkovich P;Hayes CJ;Nguyen-Van-Tam J;Brown IH;Liu J;Chang KC
除了明智地使用有效疫苗外，SARS-CoV-2和其他主要呼吸道病毒的长期控制战略还需要包括治疗急性感染的抗病毒药物。虽然正在推出COVID-19疫苗以进行大规模疫苗接种，但针对任何疾病正在使用或开发的抗病毒药物数量有限，这证明了抗病毒药物开发面临的挑战。我们最近表明，非细胞毒性水平的thapsigargin (TG)，肌浆/内质网（ER） Ca2+ atp酶泵的抑制剂，诱导有效的宿主先天免疫抗病毒反应，阻断甲型流感病毒的复制。本研究表明，TG对呼吸道合胞病毒（RSV）、普通感冒冠状病毒OC43、SARS-CoV-2和甲型流感病毒在永活细胞或原代人细胞中的复制也非常有效。甘油三酯对OC43和RSV的抑制作用明显优于瑞德西韦和利巴韦林。值得注意的是，甘油三酯在单独感染中对冠状病毒（OC43和SARS-CoV-2）和流感病毒（苏联H1N1和pdm 2009 H1N1）的抑制作用与在合并感染中一样。感染后口服耐酸甘油三酯可保护小鼠免受致命流感病毒的攻击。结合其在活性感染前或感染过程中抑制不同病毒的能力，以及暴露于TG后至少48小时的抗病毒持续时间，我们认为TG（或其衍生物）是一种有前途的广谱抑制剂，可抑制SARS-CoV-2、OC43、RSV和流感病毒。
The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.
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DOI：
10.3390/v12101093
发表时间：
2020-09-27
期刊：
Viruses
影响因子：
--
作者：
Goulding LV;Yang J;Jiang Z;Zhang H;Lea D;Emes RD;Dottorini T;Pu J;Liu J;Chang KC
通讯作者：
Chang KC
DOI：
10.1073/pnas.1811345115
发表时间：
2018-11-06
影响因子：
11.1
作者：
Goldhill DH;Te Velthuis AJW;Fletcher RA;Langat P;Zambon M;Lackenby A;Barclay WS
通讯作者：
Barclay WS
影响因子：
64.8
作者：
Riva L;Yuan S;Yin X;Martin-Sancho L;Matsunaga N;Pache L;Burgstaller-Muehlbacher S;De Jesus PD;Teriete P;Hull MV;Chang MW;Chan JF;Cao J;Poon VK;Herbert KM;Cheng K;Nguyen TH;Rubanov A;Pu Y;Nguyen C;Choi A;Rathnasinghe R;Schotsaert M;Miorin L;Dejosez M;Zwaka TP;Sit KY;Martinez-Sobrido L;Liu WC;White KM;Chapman ME;Lendy EK;Glynne RJ;Albrecht R;Ruppin E;Mesecar AD;Johnson JR;Benner C;Sun R;Schultz PG;Su AI;García-Sastre A;Chatterjee AK;Yuen KY;Chanda SK
通讯作者：
Chanda SK
影响因子：
5.2
作者：
Mirabelli, Carmen;Jaspers, Martine;Jochmans, Dirk
通讯作者：
Jochmans, Dirk
影响因子：
7.6
作者：
Brown, Ariane J.;Won, John J.;Sheahan, Timothy P.
通讯作者：
Sheahan, Timothy P.