Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates

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Abstract

Due to the complicated pathogenic pathways of coronavirus disease 2019 (COVID-19), related medicinal therapies have remained a clinical challenge. COVID-19 highlights the urgent need to develop mechanistic pathogenic pathways and effective agents for preventing/treating future epidemics. As a result, the destructive pathways of COVID-19 are in the line with clinical symptoms induced by severe acute coronary syndrome (SARS), including lung failure and pneumonia. Accordingly, revealing the exact signaling pathways, including inflammation, oxidative stress, apoptosis, and autophagy, as well as relative representative mediators such as tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), Bax/caspases, and Beclin/LC3, respectively, will pave the road for combating COVID-19. Prevailing host factors and multiple steps of SARS-CoV-2 attachment/entry, replication, and assembly/release would be hopeful strategies against COVID-19. This is a comprehensive review of the destructive signaling pathways and host–pathogen interaction of SARS-CoV-2, as well as related therapeutic targets and treatment strategies, including potential natural products-based candidates.

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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Clinical Characteristics of Coronavirus Disease 2019 in China

Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu, Dingyu Zhang, Wenling Wang … (2020)

Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)

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Author and article information

Contributors

Kyoko Nakagawa-Goto: Role: Academic Editor

Journal

Journal ID (nlm-ta): Molecules

Journal ID (iso-abbrev): Molecules

Journal ID (publisher-id): molecules

Title: Molecules

Publisher: MDPI

ISSN (Electronic): 1420-3049

Publication date (Electronic): 14 May 2021

Publication date Collection: May 2021

Volume: 26

Issue: 10

Electronic Location Identifier: 2917

Affiliations

[1 ]Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran; pharmacy.sajad@ 123456yahoo.com (S.F.); zmoradi@ 123456kums.ac.ir (S.Z.M.); sanapiri@ 123456ymail.com (S.P.)

[2 ]Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran; zeinab7641@ 123456yahoo.com

[3 ]Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran

[4 ]Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, Ankara 06330, Turkey; esrak@ 123456gazi.edu.tr

[5 ]Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8330507, Chile

[6 ]Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

[7 ]Medical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran

[8 ]Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile

Author notes

[* ]Correspondence: e.sobarzo@ 123456usc.es (E.S.-S.); mh.farzaei@ 123456gmail.com (M.H.F.); javier.echeverriam@ 123456usach.cl (J.E.)

[†]

The authors have contributed equally to this review.

Author information

Sajad Fakhri https://orcid.org/0000-0001-8265-8284

Zeinab Nouri https://orcid.org/0000-0003-2309-4081

Seyed Zachariah Moradi https://orcid.org/0000-0003-0579-3495

Esra Küpeli Akkol https://orcid.org/0000-0002-5829-7869

Eduardo Sobarzo-Sánchez https://orcid.org/0000-0002-2790-2544

Mohammad Hosein Farzaei https://orcid.org/0000-0001-7081-6521

Javier Echeverría https://orcid.org/0000-0002-1688-968X

Article

Publisher ID: molecules-26-02917

DOI: 10.3390/molecules26102917

PMC ID: 8156180

SO-VID: ec9ca293-797c-4ca5-b6ab-3f63a576f9b1

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates

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Novel Coronavirus Disease COVID-19

Most cited references 298

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Clinical Characteristics of Coronavirus Disease 2019 in China

A Novel Coronavirus from Patients with Pneumonia in China, 2019

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