阅读说明：本技术 卡非佐米作为冠状病毒广谱抑制剂的新用途 (Novel use of carfilzomib as coronavirus broad-spectrum inhibitor ) 是由 徐欢 童贻刚 范华昊 葛琳 李会强 宋立华 刘艳玲 安小平 周美玲 洪碧霞 翟丽 于 2020-06-11 设计创作，主要内容包括：本发明公布了卡非佐米的新用途,卡非佐米可作为冠状病毒的广谱抑制剂用于治疗2019新型冠状病毒感染,严重急性呼吸综合症(SARS),中东呼吸综合症(MERS)以及人冠状病毒OC43(HCoV-OC43)引发的普通感冒。卡非佐米可以结合冠状病毒的主蛋白酶(3CL pro),抑制病毒复制,是新冠病毒抑制剂,作为老药新用,卡非佐米的安全性没有问题,因此可以应用于临床。(The invention discloses a new application of carfilzomib, and the carfilzomib can be used as a broad-spectrum inhibitor of coronavirus for treating 2019 novel coronavirus infection, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and common cold caused by human coronavirus OC43(HCoV-OC 43). Carfilzomib can bind to main protease (3CL pro) of coronavirus to inhibit virus replication, is a novel coronavirus inhibitor, is used as an old medicine, has no problem in safety, and can be clinically applied.)

1. Use of carfilzomib for the manufacture of a medicament for the prevention and treatment of coronavirus infection.

2. Use according to claim 1, characterized in that: the coronavirus comprises 2019 novel coronavirus COVID-19, severe acute respiratory syndrome SARS virus, middle east respiratory syndrome MERS virus, common cold virus HCoV-OC43, human coronavirus NL63, human coronavirus 229E and human coronavirus HKU 1.

3. Use according to claim 1, characterized in that: the coronavirus comprises 2019 novel coronavirus COVID-19 and middle east respiratory syndrome MERS virus.

4. Use according to claim 1, characterized in that: the coronavirus is a 2019 novel coronavirus COVID-19.

5. Use according to any one of claims 1 to 4, characterized in that: the coronavirus infection is coronavirus pneumonia or common cold.

6. Use according to any one of claims 1-2, characterized in that: the coronavirus infection comprises 2019 novel coronavirus COVID-19 pneumonia, severe acute respiratory syndrome SARS, middle east respiratory syndrome MERS, common cold, human coronavirus NL63 pneumonia, human coronavirus 229E pneumonia, and human coronavirus HKU1 pneumonia.

7. Use according to any one of claims 1 to 3, characterized in that: the coronavirus infection comprises 2019 novel coronavirus COVID-19 pneumonia and middle east respiratory syndrome MERS.

8. Use according to any one of claims 1 to 4, characterized in that: the coronavirus infection is 2019 novel coronavirus COVID-19 pneumonia.

9. Use according to any one of claims 1 to 4, characterized in that: rutin can bind to coronavirus main protease 3 CLpro.

10. Use according to any one of claims 1 to 4, characterized in that: rutin can combine with 2019 coronavirus main protease 3CLpro of novel coronavirus COVID-19.

Technical Field

The invention belongs to the field of medicines, relates to a new application of carfilzomib, and particularly relates to an application of carfilzomib in preventing or treating coronavirus infection.

Background

Highly pathogenic coronavirus infection has become a public health concern over the last decade. Severe acute respiratory syndrome (SARS, 2002-2004), middle east respiratory syndrome (MERS, 2012-to-date), 2019 novel coronaviruses (2019-nCoV, COVID-19), each of which has a tremendous impact on human health and economic development.

Because there are no effective drugs and vaccines, the research and development of new drugs for new coronavirus is of great significance, and in the war without smoke, a plurality of scientific research institutions and pharmaceutical companies around the world are dedicated to research and develop new coronavirus vaccines and therapeutic drugs. Therefore, the invention has great social and economic significance.

Carfilzomib, is a proteasome inhibitor and is indicated for the treatment of multiple myeloma patients. Multiple Myeloma (MM) is a malignant tumor derived from a B cell line, characterized by clonal proliferation of malignant plasma cells in the bone marrow environment, causing bone fractures and bone marrow failure, is the second most common hematological tumor worldwide and incurable by conventional chemotherapy regimens.

Bortezomib (brotezomib) is the first proteasome inhibitor and the first-line drug for multiple myeloma, so that the treatment of multiple myeloma has breakthrough progress, and due to strong drug resistance and continuous research on the drug resistance mechanism of people, carfilzomib is approved as the second protease inhibitor by the FDA after bortezomib, and is used for treating multiple myeloma patients who receive at least 2 drugs (including bortezomib and immunomodulator therapy) before treatment. Carfilzomib is a specific, irreversible targeted inhibitor, originally developed by Proteolix corporation, produced by ornix (Onyx) pharmaceutical corporation, approved by FDA for marketing at 2012, 7/20.

Disclosure of Invention

The purpose of the present invention is to provide an effective inhibitor for a coronavirus including a 2019 novel coronavirus (COVID-19), which can prevent and treat an infection with a coronavirus including a 2019 novel coronavirus. The invention provides a new application of carfilzomib, which is an effective inhibitor of coronavirus including 2019 novel coronavirus, and an application of carfilzomib in preparation of a medicine for preventing or treating coronavirus infection.

The application is that the coronavirus comprises 2019 novel coronavirus (COVID-19), Severe Acute Respiratory Syndrome (SARS) virus, Middle East Respiratory Syndrome (MERS) virus, common cold human coronavirus OC43(HCoV-OC43), human coronavirus NL63(HCoV-NL63), human coronavirus 229E (HCoV-229E) and human coronavirus HKU1(HCoV-HKU 1).

The application, wherein the coronavirus is 2019 novel coronavirus (COVID-19).

The use wherein the coronavirus infection is coronavirus pneumonia or common cold.

The application, wherein the coronavirus infection comprises 2019 novel coronavirus COVID-19 pneumonia, severe acute respiratory syndrome SARS, middle east respiratory syndrome MERS, common cold, human coronavirus NL63 pneumonia, human coronavirus 229E pneumonia, and human coronavirus HKU1 pneumonia.

The use of (b), wherein the coronavirus infection is 2019 novel coronavirus pneumonia.

The inventor finds that: carfilzomib binds 2019 the coronavirus main protease (3CLpro) of the novel coronavirus, interferes with cleavage of the RNA virus precursor protein, and inhibits viral replication.

2019 the novel coronavirus enters the cell and recognizes the receptor ACE2 by virtue of spike protein spike, and two key proteases participating in the proteolysis process of 2019-nCov are coronavirus main protease (3CLpro) and papain-like protease (PLpro) respectively. The 3CL protease is a key protease for catalyzing the cleavage of RNA virus precursor protein and has an important function on the replication of the virus. Therefore, small molecule inhibitors targeting the 3CLpro protein can be applied in therapy against novel coronaviruses.

The inventors have also found that carfilzomib binds equally well to the 3CL target protein of MERS. The 3CL protease is a key protease for catalyzing the cleavage of RNA virus precursor protein and has an important function on the replication of the virus. Thus, nelfinavir can be applied in the treatment of individual subtype coronavirus infections.

The compounds of the present invention may be formulated into various suitable pharmaceutical preparation forms. Can be used alone or mixed with medicinal adjuvants (such as excipient, diluent, etc.) to make into oral tablet, capsule, granule or syrup, or powder for injection or solution.

Compared with the prior art, the invention has the following technical effects:

carfilzomib can inhibit coronavirus main protease (3CLpro) at cellular level, and obviously inhibit virus replication, thereby preventing or treating coronavirus pneumonia infection and common cold.