Progress in Microbes and Molecular Biology Review Article 1 Novel coronavirus 2019-nCoV: Could this virus become a possible global pandemic Vengadesh Letchumanan1a*,Nurul-Syakima Ab Mutalib2a, Bey-Hing Goh3, Learn-Han Lee1* 1Novel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. 2UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, University Kebangsaan Malaysia, Kuala Lum- pur, Malaysia 3Biofunctional Molecule Exploratory Research Group (BMEX), School of Pharmacy, Monash University Malaysia, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia. aThe authors contributed equally to the writing of this review Abstract: In December 2019, the emerging of a new coronavirus-induced pneumonia created a distress among people in China and the international community. This virus was identified as novel coronavirus 2019-nCoV. At the time this Review went to press, the virus has spread to across 27 countries, infecting 17,488 people and caused 362 deaths. The transmission of 2019-nCoV to individuals of different countries is predominantly through close contact with an infected person. Based on the available data, there is a rising trend of infected and death cases. At this point, there is no specific drug or vaccine to treat infected patients besides supportive care. Nevertheless, researchers and doctors around the world have reported the success of using existing antiviral drugs to treat patients. Keywords: Novel Coronavirus, 2019-nCoV, supportive care, global pandemic, treatment Received: 3rd February 2020 Accepted: 5th February 2020 Published Online: 6th February 2020 Citation: Letchumanan V, Ab Mutalib N-S, Goh B-H, et al. Novel Coronavirus 2019-nCoV: Could this virus become a pos- sible global pandemic. Prog Microbes Mol Biol 2020; 3(1): a0000068. https://doi.org/10.36877/pmmb.a0000068 INTRODUCTION A new year and a new decade kicked off with a global health threat and challenge, the novel coronavirus 2019- nCoV. News emerged in early December 2019 of pneu- monia outbreak by an unknown aetiology, where it is believed to be contracted at Wuhan’s Huanan Seafood Wholesale Market[1]. On 31st December 2019, the World Health Organization (WHO)’s Chinese office was notified of pneumonia cluster cases, which led to the closing of the market on 1st January 2020[1]. The Chinese authorities and WHO identified it as a new type of coronavirus, better known as 2019-nCoV[2]. The 2019-nCoV virus belongs to same coronavirus family which includes the Severe Acute Respiratory Syndrome (SARS) — the virus that caused an eventual 8,096 cases and 744 deaths in 2002-2003[3]. The virus became an instant hot news and raised the fear of the international community. The health organizations along with scientists and clini- cians worked around the clock to uncover the information of 2019-nCoV. Within days of detecting the initial cluster of cases, the complete genome sequence of 2019-nCoV with a sequence length of 29,903bp was deposited on GenBank and Global Initiative on Sharing All Influ- enza Data (GISAID)[4,5]. The genome sequence infor- mation is beneficial in the development of primers for surveillance tests and diagnostic kits[3]. Pharmaceutical companies and researchers around the world have been working on different approaches to produce an effective drug or vaccine for 2019-nCoV[6]. These efforts acceler- ated after over 30 genome sequence of 2019-nCoV have been publicly deposited in GenBank (Table 1)[7]. Table 1. Genome sequence of 2019-nCoV deposited in GenBank. GenBank Accession Gene Region Locality MT008023 M Italy, Rome MT008022 M Italy, Rome MT007544 complete Australia MN997409 complete USA MN996531 complete Wuhan MN996530 complete Wuhan Copyright 2019 by Letchumanan V et al. and HH Publisher. This work under licensed under the Creative Commons Attribution-Non- Commercial 4.0 International Lisence (CC-BY-NC 4.0) *Correspondence: Learn-Han Lee, Jeffrey Cheah School of Med- icine and Health Sciences, Monash University Malaysia, Selan- gor, Malaysia; lee.learn.han@monash.edu; leelearnhan@yahoo. com. Vengadesh Letchumanan, Jeffrey Cheah School of Medi- cine and Health Sciences, Monash University Malaysia, Selan- gor, Malaysia. vengadesh.letchumanan1@monash.edu 2 MN996529 complete Wuhan MN996528 complete Wuhan MN996527 complete Wuhan MN994468 complete USA MN994467 complete USA MN988713 complete USA MN988669 complete China MN988668 complete China MN985325 complete USA MN975268 S China MN975267 S China MN975266 S China MN975265 RdRP China MN975264 RdRP China MN975263 RdRP China MN975262 complete China MN970004 RdRP Thailand MN970003 RdRP Thailand MN938390 S Shenzhen RdRP:RNA-dependent RNApolymerase; S: Surface EPIDEMIOLOGY 2019-nCoV reservoir Researchers compared the genome sequence of 2019- nCoV with a viral database and suggest it belongs to betacoronavirus originated from bats. However, the spe- cific wildlife host as virus reservoir is yet to be confirmed since various live animals was sold at the market[8,9]. A comprehensive genome sequence analysis was carried out by researchers from Beijing, China to determine the possible animal reservoir. Their evolutionary analysis suggested that snakes are the most likely wildlife animal as virus reservoir for 2019-nCoV[10]. Conversely, scien- tists affiliated with UK-based universities disputed the findings by Chinese researchers, and affirmed that 2019- nCoV is most closely related to bats[11]. Zhou and col- leagues from China also reported this virus is potentially bat origin[12]. Pushing aside on the debate whether bats or snakes are the real culprit of 2019-nCoV, this zoonotic vi- rus has spread to over twenty-seven countries worldwide. The spreading Wuhan, the epicenter has been left deserted amid the deadly coronavirus-induced pneumonia outbreak. In aim to contain the virus spread, the local authorities ordered a city-wide lockdown in Wuhan, the sprawling capital of Central China’s Hubei province on 23 January 2020[1,13]. Although, early reports revealed limited human to human spread, but the recent drastic increase of infected cases proven the latter assumption was wrong. It is indeed a human-to-human transmission and the virus is spreading in a fast pace to other Chinese cities, Asian countries and other parts of the world[14,15] (Table 2). This fast-spreading virus has claimed 362 lives and infected 17,488 people in 27 countries at the time this Editorial went to press (Figure 1). China tops all the countries with over 17,000 infected patients and 361 deaths (Table 3), this figure in- creases daily with an estimated transmission rate/basic reproductive number (Ro) 3.0-4.0 (3–4 newly infected cases from 1 case)[16]. On 2nd February 2020, a death of a 44-year-old Chinese man from Wuhan in Philippines marked the first death that occurred outside of China. The patient showed initial signs of improvement, how- ever his condition deteriorated within the last 24 hours and he succumbed[17]. The concern raises as transmission of 2019-nCoV to other countries besides China is mainly by people who have travelled from the epicenter of the outbreak or had close contact with an infected person. For instance, in Malaysia, eight confirmed cases are patients of China nationality, and they have been under isolation hospitalization until fully recover from the infection. Of note, based on the existing epidemiological data, the incu- bation period of this virus is 14 days. 2019-nCoV: Could this... Figure 1. Illustration of novel coronavirus 2019-nCoV transmission across the global. As of 3 February 2020 , this virus has spread to over 27 countries and alarming a fear to the international community. 3 Table 2. The worldwide spread of coronavirus 2019-nCoV. Countries Confirmed Cases Death Cured China 17,302 361 512 Hong Kong 15 Taiwan 10 Japan 20 1 Thailand 19 7 Singapore 18 Korea 15 Australia 12 2 Germany 10 Malaysia 8 US 11 Vietnam 8 1 France 6 United Arab Emirates 5 Canada 4 India 3 Italy 2 Philippines 2 1 Russia 2 UK 2 Cambodia 1 Finland 1 Nepal 1 Spain 1 Sri Lanka 1 1 Sweden 1 Macau 8 Source: National Health Commission of the People’s Republic of China and Worl- dometer on Wuhan coronavirus outbreak - https://www.worldometers.info/corona- virus/. Table 3. The spread of coronavirus 2019-nCoV in China. Province Confirmed Cases Death Cured Hubei 11177 350 295 Zhejiang 724 36 Guangdong 725 14 Henan 566 2 15 Hunan 521 17 Anhui 408 8 Jiangxi 391 18 Chongqing 312 2 8 Jiangsu 271 7 Szechuan 254 1 13 Shandong 259 7 Beijing 212 1 12 Shanghai 203 1 10 Fujian 179 Shaanxi 128 Guangxi 127 7 Yunnan 114 5 Hebei 113 1 3 Heilongjiang 118 2 2 Liaoning 74 1 Hainan 70 1 4 Shanxi 66 2 Tianjin 56 1 Ganxu 51 3 Guizhou 46 2 Ningxia 31 Inner Mongolia 34 1 Jilin 31 1 Xinjiang 24 Hong Kong 15 Qinghai 13 Taiwan 10 Macau 8 Tibet 1 Source: National Health Commission of the People’s Republic of China, as of 3rd February 2020 Letchumanan V et al. 4 MANAGEMENT MEASURES Lock-down and medical facilities The occurrence of this virus has placed the Chinese gov- ernment in a strong crisis management and preparedness for a pandemic. The government imposed a complete lock- down of Wuhan and about a dozen of other cities, in an attempt to prevent the virus from spreading further within China. The effectiveness of this implementation has been disputed by many experts globally. Professor Chandy John, a former president of America Society of Tropical Medi- cine and Hygiene mentioned that a number of potential issues may arise including basic human rights concern, inadequate healthcare facilities or medication for the sick people, and people who aren’t sick — unable to leave and may fall ill after exposure to the virus. However, he still agrees that prevention of travel is one the effective way to contain the virus and reduce the transmission[18]. Like- wise, a bioethicist at New York University also expressed an agreement for Wuhan quarantine and added that it is a prudent action implemented by the government[18]. Since the majority of infected cases are in Wuhan, the Chinese government has invested huge capital in building two new hospitals: Huoshenshan Hospital and Leishen- shan Hospital that would be operational in early February 2020[19,20]. In addition, the Chinese government has ap- proved the sale of two virus detection kits and a sequenc- ing system by genomic company BGI Group, to aid and enhance the identification of this novel virus. According to BGI sources, their test kit is able to identify the novel 2019-nCoV within three hours, while the other kit can as- sist to differentiate and the diagnose infections. One hun- dred thousand test kits have been dispatched to the coun- try’s worst hit regions[21]. Global effort and protection measures In other parts of the nation and several countries has taken precaution measures to control the spread of coronavirus. Health screening in all entry and exit points (airports, port terminals, train stations) have been beef-up in effort to contain the virus[22]. Passengers who present any clinical symptoms of fever, flu and cough, are placed in an isolation and quarantine for further evaluation and treatments. Many airlines have also drawn-up preventive measures by not providing hot meals, blankets and newspapers in the plane, in aim to contain the virus and reduce the personal contact among passengers[23]. The healthcare organization has been promoting awareness and preventive measures that should be followed by the members of the public. People should adopt good hygiene practice by washing their hands with water and soap, or use hand sanitizer, always wear a mask, avoid crowded public locations, and avoid close contact with any infected person. A person should directly report to their respective healthcare centers if they are presenting any symptoms and other risk factors of 2019-nCoV infec- tion including had a travel history or close contact with a confirmed patient. The novel coronavirus 2019-nCoV has created an impact to the public healthcare and to our community. In a recent interview, Dr Huang Chaolin, the vice director of Wuhan Jinyintan Hospital, revealed that there might be multiple places where the virus was first originated and transmit- ted to humans[24]. It is because the first few patients who was admitted at the hospital had no direct exposure to Wuhan’s Huanan Seafood Wholesale Market, which was considered the primary source of the epidemic. Judging from the whole situation, there could be multi- sources, nonetheless the authorities have no clue about other sources. The Chinese Center for Disease Control and Prevention have collected environmental samples from Wuhan’s Huanan Seafood Wholesale Market, and over thirty samples were found to contain the nucleic acid of the virus. If the virus is from multi-sources, ex- perts warned the situation would become worsen in the coming days if efforts taken to contain the virus are inef- fective[24]. Treatment options Currently, there is no specific drug or vaccine avail- able to treat this virus infection besides supportive care. A patient will present symptoms of fever, fatigue, dry cough, shortness of breath, runny nose and sore throat [25]. Patients with underlying comorbidities for example diabetes, hypertension, chronic lung disease, asthma, cardiovascular diseases, and immunocompromised are prone for severe complication of 2019-nCoV infection [25,26]. Hence, the older group and children are advice to take extra precaution measures to avoid been contract with 2019-nCoV. In hospitals, doctors are doing their best to treat and save the lives of their patients, without the effective drug or vaccine. Doctors from Thailand successfully treated a 71-year-old patient with a combination of antivirals that used to treat flu (oseltamivir) and HIV (lopinavir and ritonavir) [27]. Where else, in The United States (US), doctors treated a 2019-nCoV positive patient with ex- perimental Gilead Sciences drug - remdesivir. Remde- sivir was given to the 35-year-old patient and his symp- toms improved without any side effects [28]. Although the combinations of antiviral treatments have shown posi- tive effect in treating 2019-CoV patients, further tests should be done to confirm the effectiveness of these an- tivirals. Hopefully, this novel coronavirus does not ex- hibit any resistance phenotype towards flu antivirals e.g. oseltamivir-resistance, which was observed previously in influenza A H7N9 virus [29]. Conclusion The rapid rising of infected cases and deaths alarm ex- perts, who fear the virus 2019-nCoV would likely be- come a pandemic across the globe. The lethally of this new virus is yet to be known, but now findings suggest that the virus may be spreading from person to person via the digestive system [30,31]. There is an increasing trend of infected cases in China and around the world- wide countries. Nevertheless, the China government, WHO and respective healthcare bodies are doing their best to understand and manage the coronavirus out- break. On 30th January 2020, WHO declared the novel 2019-nCoV coronavirus outbreak as a Public Health Emergency of International Concern (PHEIC), and this brings an impact to China and international community 2019-nCoV: Could this... 5 [32,33]. The PHEIC will see the mobilization of international response to work to together to contain the virus threat. Hopefully, this announcement would help with controlling the spread of the virus. In view of the present virus outbreak, the community should adapt to the new lifestyle changes. Social distanc- ing must be a part of their daily life. Avoid being proxim- ity with people, mass gatherings, and functions. In certain countries, their public has the tendency to greet others by hugging or a handshake. Without realizing, they probably might be spreading or contracting the virus by their ac- tions. Now, we may want to stop this culture for the time being. Another aspect is self-quarantine if one exhibit any symptoms of infection or had a close contact with a con- firmed patient. This measure is proven to be an effective tool to contain the spread of any airborne virus. The nation may feel stressed and unpleasant if a lock-down is imposed in their country or asked to wear mask. Look- ing back at history, lock-down and wearing mask was seen to be an effective step implemented by Dr Wu Lien-teh in effort to control the spread of pneumonic plague virus in 1910. Dr Wu Lien-teh, a Malaysian born doctor gained fame by ending the pneumonic plague in China and en- couraging people at that time to wear gauze-and-cotton masks, controlled the people’s movement, instructed to hospitalize all infected patients, carried out disinfection in open areas, mass burials of the deaths, and prohibited close contact [34]. His endless effort managed to contain the plague within seven months (March 1911). In summary, the novel coronavirus 2019-nCoV outbreak is a reminder to the international community of an emerg- ing virus infection that need constant surveillance, rapid diagnosis, and robust research to understand the biology features of this novel virus. There is a possibility this novel coronavirus would become a global pandemic which the se- verity and people’s susceptibility is yet to be forecasted by the experts. If it becomes a pandemic, the developing coun- tries may not have enough resources to cope this deadly vi- rus. In addition, countries may experience severe setbacks as the world economic may paralyze and will take months for the recovery. Hence, the world should get prepared with adequate preventive measures to contain the spread of this deadly virus. The international community should have the preparedness for a possible pandemic outbreak and ad- here to all the precaution measures. The healthcare sector should develop effective countermeasures and ensure all medical resources like masks. PPEs, and ventilators are readily available in all hospitals. Well, it is rather safer to be over prepared than being under prepared on facing this novel coronavirus 2019-nCoV. Conflict of Interest The authors declare that there is no conflict of interest in this work. Author Contributions VL and N-SAM performed the literature search, critical data analysis and writing of this review. Technical support and proofreading was contributed by B-HG and L-HL. This review writing was founded by L-HL. 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