biomolecules Editorial Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks † Murat Seyran 1, Sk. Sarif Hassan 2 , Vladimir N. Uversky 3,* , Pabitra Pal Choudhury 4, Bruce D. Uhal 5 , Kenneth Lundstrom 6,*, Diksha Attrish 7, Nima Rezaei 8,9, Alaa A. A. Aljabali 10 , Shinjini Ghosh 11, Damiano Pizzol 12 , Parise Adadi 13 , Tarek Mohamed Abd El-Aziz 14,15 , Ramesh Kandimalla 16, Murtaza M. Tambuwala 17 , Amos Lal 18, Gajendra Kumar Azad 19 , Samendra P. Sherchan 20, Wagner Baetas-da-Cruz 21 , Giorgio Palù 22,* and Adam M. Brufsky 23 1 Doctoral Studies in Natural and Technical Sciences (SPL 44), University of Vienna, Währinger Straße, A-1090 Vienna, Austria; [email protected] 2 Department of Mathematics, Pingla Thana Mahavidyalaya, Maligram, Paschim Medinipur 721140, West Bengal, India; [email protected] 3 Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA 4 Applied Statistics Unit, Indian Statistical Institute, Kolkata 700108, West Bengal, India; [email protected] 5 Department of Physiology, Michigan State University, East Lansing, MI 48824, USA; [email protected] 6 PanTherapeutics, Rte de Lavaux 49, CH1095 Lutry, Switzerland 7 Dr. B R Ambedkar Center for Biomedical Research (ACBR), University of Delhi (North Camps), Delhi-110007, India; [email protected] 8 Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran, Citation: Seyran, M.; Hassan, S..S.; University of Medical Sciences, Tehran 1419733151, Iran; [email protected] Uversky, V.N.; Pal Choudhury, P.; 9 Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education Uhal, B.D.; Lundstrom, K.; Attrish, D.; and Research Network (USERN), Tehran 1419733151, Iran Rezaei, N.; Aljabali, A.A.A.; Ghosh, S.; 10 Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University-Faculty of Pharmacy, et al. Urgent Need for Field Surveys Irbid 566, Jordan; [email protected] 11 of Coronaviruses in Southeast Asia to Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Understand the SARS-CoV-2 Kolkata 700009, West Bengal, India; [email protected] 12 Phylogeny and Risk Assessment for Italian Agency for Development Cooperation—Khartoum, Sudan Street 33, Al Amarat 13374, Sudan; [email protected] Future Outbreaks . Biomolecules 2021, 13 Department of Food Science, University of Otago, Dunedin 9054, New Zealand; [email protected] 11, 398. https://doi.org/10.3390/ 14 Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, biom11030398 7703 Floyd Curl Dr, San Antonio, TX 78229-3900, USA; [email protected] 15 Zoology Department, Faculty of Science, Minia University, El-Minia 61519, Egypt Received: 10 January 2021 16 CSIR-Indian Institute of Chemical Technology Uppal Road, Tarnaka, Accepted: 20 February 2021 Hyderabad 500007, Telangana State, India; [email protected] Published: 9 March 2021 17 School of Pharmacy and Pharmaceutical Science, Ulster University, Coleraine BT52 1SA, Northern Ireland, UK; [email protected] 18 Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA; Publisher’s Note: MDPI stays neutral [email protected] with regard to jurisdictional claims in 19 Department of Zoology, Patna University, Patna 800005, Bihar, India; [email protected] published maps and institutional affil- 20 Department of Environmental Health Sciences, Tulane University, New Orleans, LA 70112, USA; iations. [email protected] 21 Translational Laboratory in Molecular Physiology, Centre for Experimental Surgery, College of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941901, Brazil; [email protected] 22 Department of Molecular Medicine, University of Padova, Via Gabelli 63, 35121 Padova, Italy 23 UPMC Hillman Cancer Center, Department of Medicine, Division of Hematology/Oncology, University of Copyright: © 2021 by the authors. Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; [email protected] Licensee MDPI, Basel, Switzerland. * Correspondence: [email protected] (V.N.U.); [email protected] (K.L.); [email protected] (G.P.) This article is an open access article † All authors are the members of the Self-Assembled COVID Research and Education Directive distributed under the terms and (SACRED) Consortium. conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ Phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 (SARS- 4.0/). CoV-2) is focused on a single isolate of bat coronaviruses (bat CoVs) which does not Biomolecules 2021, 11, 398. https://doi.org/10.3390/biom11030398 https://www.mdpi.com/journal/biomolecules Biomolecules 2021, 11, x FOR PEER REVIEW 2 of 7 Phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) is focused on a single isolate of bat coronaviruses (bat CoVs) which does not ade- Biomolecules 2021, 11, 398 2 of 7 quately represent genetically related coronaviruses (CoVs). The unique bat CoV RaTG13 is the only identified sequence genetically associated with SARS-CoV-2. Data scarcity of bat CoV sequences raises concerns over several fundamental experimental and biostatis- adequatelytical aspects, represent e.g., repeatability genetically related of sequences coronaviruses and (CoVs). intraspecies The unique variations bat CoV RaTG13in critical gene is the only identified sequence genetically associated with SARS-CoV-2. Data scarcity of bat regions, such as the receptor-binding domain of the spike protein. The Sunda pangolin CoV sequences raises concerns over several fundamental experimental and biostatistical aspects,has been e.g., proposed repeatability as the of sequencesintermediate and intraspecieshost and source variations of SARS-CoV-2, in critical gene but regions, no pangolin suchCoV asisolates the receptor-binding have been reported domain ofin theits spikehabitats protein. in Southeast The Sunda Asia. pangolin Most has pangolin been CoVs proposedwere isolated as the from intermediate pangolins host captured and source during of SARS-CoV-2, illegal animal but no trafficking, pangolin CoV raising isolates questions haveabout been such reported isolates’ in reliability its habitats and in Southeast quality. Problems Asia. Most with pangolin pangolin CoVs CoV were sampling isolated are also fromrelated pangolins to the capturedsubstandard during quality illegal of animal deposite trafficking,d sequences. raising There questions is an about urgent such need for isolates’field surveys reliability of bat and CoVs quality. and Problems possible with intermediate pangolin CoV hosts, sampling such as are pangolins, also related ferrets, to and thecivets, substandard in Southeast quality Asia of depositedto investigate sequences. the genomic There is source an urgent of SARS-CoV-2 need for field surveysand assess pos- of bat CoVs and possible intermediate hosts, such as pangolins, ferrets, and civets, in sible future risks for new outbreaks. Southeast Asia to investigate the genomic source of SARS-CoV-2 and assess possible future risks forSARS-CoV-2 new outbreaks. is the causative agent of the coronavirus disease 2019 (COVID-19) pan- demicSARS-CoV-2 in which isthe the first causative cases agentwere of reported the coronavirus in Wuhan, disease Hubei 2019 (COVID-19)Province, China. pan- SARS- demicCoV-2, in a whichmember the of first Betacoronavirus cases were reported and subgenus in Wuhan, Sarbecovirus Hubei Province,, is phylogenetically China. SARS- related CoV-2,to bat acoronaviruses member of Betacoronavirus (bat CoVs)and RaTG13 subgenus (detectedSarbecovirus in Pu’er, is phylogenetically City in 2013) related and RmYN02 to(detected bat coronaviruses in Xishuangbanna (bat CoVs) City RaTG13 in 2019) (detected and were in Pu’er detected City inapproximately 2013) and RmYN02 2000 km from (detectedWuhan [1,2]. in Xishuangbanna Betacoronavirus City and in 2019) its genetic and were reservoir detected bat approximately species, such 2000 as kmthe fromintermediate Wuhanhorseshoe [1,2]. batBetacoronavirus Rhinolophusand affinis its genetic, inhabit reservoir Southeast bat species,Asia [1,3,4 such]. as It thehas intermediate been hypothesized horseshoe bat Rhinolophus affinis, inhabit Southeast Asia [1,3,4]. It has been hypothesized that pangolin CoVs may have originated from cross-species transmission in bats [5]. To that pangolin CoVs may have originated from cross-species transmission in bats [5]. To date,date, no no additional additional bat bat CoVs CoVs RaTG13 RaTG13 or RmYN02 or RmYN02 isolates isolates and no and pangolin no pangolin CoV isolates CoV isolates originatingoriginating from from healthy healthy or sickor sick pangolins pangolins in their in their natural natural habitats habitats in Southeast in Southeast Asian Asian countriescountries have have been been sequenced sequenced (Figure (Figure1). Therefore, 1). Ther here,efore, we here, seek towe draw seek the to attentiondraw the of attention relevantof relevant institutions institutions toward toward the need the to need obtain to CoVobtain isolates CoV fromisolates potential from hosts,potential such hosts, as such healthyas healthy or sick or pangolins,sick pangolins, in their in natural their natura habitatsl habitats to