Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19.
Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19.
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DOI：
10.1016/j.compbiomed.2020.104051
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发表时间：
2020-11
影响因子：
7.7
通讯作者：
Ghosh P
中科院分区：
文献类型：
--
作者：
Barh D;Tiwari S;Weener ME;Azevedo V;Góes-Neto A;Gromiha MM;Ghosh P
SARS-CoV-2已在全球范围内大流行，目前尚无有效药物。尽管FDA批准的几种药物目前正在进行药物重新定位的临床试验，但全球正在努力进行新药鉴定。在本文中，使用多组学（相互作用组，蛋白质组，转录组和书目组）数据和随后的综合分析，我们提出了与SARS-CoV-2感染相关的生物学事件，并确定了几个候选药物对这种病毒性疾病。我们发现：（i）基于相互作用体的感染途径不同于其他三种基于组学的概况。(ii)病毒过程、mRNA剪接、细胞因子和干扰素信号传导以及泛素介导的蛋白水解是SARS-CoV-2感染的重要途径。(iii)SARS-CoV-2感染还与甲型流感、EB病毒、HTLV-I、麻疹和肝炎病毒共享途径。(iv)此外，细菌、寄生虫和原生动物感染途径如结核病、疟疾和利什曼病也由该病毒共享。(v)共确定了50种候选药物，包括预防剂和途径特异性抑制剂。(vi)倍他米松、雌激素、辛伐他汀、氢化可的松、托西莫单抗、环孢菌素A等是重要的药物。(vii)臭氧、一氧化氮、血浆成分和光敏剂药物也被确定为可能的治疗候选物。（viii）姜黄素、视黄酸、维生素D、砷、铜和锌可以是候选预防剂。在我们鉴定的药物中，近70%先前被认为具有抗COVID-19作用或正在进行临床试验。在我们确定的药物中，尚未测试的药物需要谨慎验证，而这些候选药物与SARS-CoV-2特异性抗病毒剂的适当药物组合沿着需要有效的COVID-19管理。SARS-CoV-2共享流感、EBV、HTLV-I、麻疹和肝炎病毒感染途径。SARS-CoV-2还具有结核病、疟疾和利什曼病感染途径。mRNA剪接、细胞因子和IFN信号传导以及泛素是重要的途径。贝伐他汀、雌激素、他汀、托西莫单抗、环孢菌素A是首选药物。臭氧、一氧化氮、血浆成分和光敏剂药物对COVID-19也很重要。姜黄素、视黄酸、维生素D、砷、铜和锌是候选预防剂。
SARS-CoV-2 has ushered a global pandemic with no effective drug being available at present. Although several FDA-approved drugs are currently under clinical trials for drug repositioning, there is an on-going global effort for new drug identification. In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. We found that: (i) Interactome-based infection pathways differ from the other three omics-based profiles. (ii) Viral process, mRNA splicing, cytokine and interferon signaling, and ubiquitin mediated proteolysis are important pathways in SARS-CoV-2 infection. (iii) SARS-CoV-2 infection also shares pathways with Influenza A, Epstein-Barr virus, HTLV-I, Measles, and Hepatitis virus. (iv) Further, bacterial, parasitic, and protozoan infection pathways such as Tuberculosis, Malaria, and Leishmaniasis are also shared by this virus. (v) A total of 50 candidate drugs, including the prophylaxis agents and pathway specific inhibitors are identified against COVID-19. (vi) Betamethasone, Estrogen, Simvastatin, Hydrocortisone, Tositumomab, Cyclosporin A etc. are among the important drugs. (vii) Ozone, Nitric oxide, plasma components, and photosensitizer drugs are also identified as possible therapeutic candidates. (viii) Curcumin, Retinoic acids, Vitamin D, Arsenic, Copper, and Zinc may be the candidate prophylaxis agents. Nearly 70% of our identified agents are previously suggested to have anti-COVID-19 effects or under clinical trials. Among our identified drugs, the ones that are not yet tested, need validation with caution while an appropriate drug combination from these candidate drugs along with a SARS-CoV-2 specific antiviral agent is needed for effective COVID-19 management. SARS-CoV-2 shares Influenza, EBV, HTLV-I, Measles, and Hepatitis virus infection pathways. SARS-CoV-2 also shares Tuberculosis, Malaria, and Leishmaniasis infection pathways. mRNA splicing, cytokine and IFN signaling, and ubiquitin are important pathways. Betamethasone, Estrogen, Statin, Tositumomab, Cyclosporin A are top candidate drugs. Ozone, Nitric oxide, plasma components, and photosensitizer drugs are also important against COVID-19. Curcumin, Retinoic acids, Vitamin D, Arsenic, Copper, and Zinc are candidate prophylaxis agents.
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