Asian Pacific Journal of Tropical Medicine

: 2021  |  Volume : 14  |  Issue : 2  |  Page : 49--51

Addressing demand for recombinant biopharmaceuticals in the COVID-19 era

Balamurugan Shanmugaraj, Waranyoo Phoolcharoen 
 Research Unit for Plant-produced Pharmaceuticals; Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

Correspondence Address:
Waranyoo Phoolcharoen
Research Unit for Plant-produced Pharmaceuticals; Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok

How to cite this article:
Shanmugaraj B, Phoolcharoen W. Addressing demand for recombinant biopharmaceuticals in the COVID-19 era.Asian Pac J Trop Med 2021;14:49-51

How to cite this URL:
Shanmugaraj B, Phoolcharoen W. Addressing demand for recombinant biopharmaceuticals in the COVID-19 era. Asian Pac J Trop Med [serial online] 2021 [cited 2023 Jun 6 ];14:49-51
Available from:

Full Text

 1. COVID-19 pandemic

The emergence and re-emergence of infectious diseases in recent years demand national health care systems to develop effective surveillance mechanisms, diagnostic, treatment, and preventive strategies. The last two decades witnessed the outbreak of several viral infections with epidemic and pandemic potentials, most of which are zoonotic. These include severe acute respiratory syndrome-coronavirus (SARS-CoV), avian and swine-origin influenza viruses, Middle East respiratory syndrome-coronavirus, Ebola, Chikungunya, Zika, Nipah, and, more recently, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)[1]. SARS-CoV-2 represents family Coronaviridae, subfamily Orthocoronavirinae, and genus Betacoronavirus. By early November 2020, there have been more than 50 million confirmed cases of COVID-19 globally, with over 1 million reported deaths[2]. The ability of the virus to spread from person to person and the mortality associated with the infection pose serious threats to public health globally. The outbreak also had a major impact on global economy and lifestyle of human populations. The pathogenesis and transmission cycle of SARS-CoV-2 has not been elucidated completely, which hampers the development of effective treatment and preventive measures.

 2. Need for affordable biopharmaceuticals

Currently, the global priority is to develop effective vaccines to control this pandemic[3]. Several candidates have been evaluated to develop effective vaccines, therapeutic or rapid diagnostic tests against SARS-CoV-2. More than 100 vaccine candidates are in different stages of testing viz., pre-clinical and clinical trials. Although developing a rapid diagnostic kit, vaccine or therapeutics is critical during the pandemic, the major challenge is to guarantee the distribution, accessibility, and availability of the vaccine/ therapeutics to everyone around the world at an affordable price. Now the biggest challenge for all the governments and international organizations is to provide and ensure equal access to medical care for their citizens.

Today, most of the recombinant pharmaceutical proteins are produced by using mammalian, bacteria, and yeast cell cultures, which is often expensive to maintain and requires high capital investment. In middle-income and low-income countries, the demand for vaccine antigens, therapeutic antibodies, or other high-value molecules is often higher than the available production capacity, which hinders the accessibility of vaccines by the poor[4]. Furthermore, the obstacles such as limited budget, poor healthcare services, non-affordability of vaccine, drugs and other biopharmaceuticals or lack of investment for developing new vaccine results in an increased burden of infectious diseases in such countries.

 3. Plant expression platform

In recent years, plants have been considered as a potential alternative to produce “high-value” foreign proteins rapidly at an affordable cost. The production of high-value recombinant proteins in plants is termed as “plant molecular farming”. The history of plant molecular farming started back in the late 1980s after the report on successful expression of recombinant antibodies in plants[5]. Since then, several proteins have been produced and many are close to commercialization. The unique advantages of plant platform over other conventional production systems include increased protein yield, lower risk of contamination, sterility is not issue during production, reduced production cost, post-translational modifications of recombinant proteins with minor differences in glycosylation, safety, flexibility, speed of production and scalability[6],[7],[8]. A vast amount of literature has shown the potential of plant-based systems for the production of recombinant biopharmaceuticals. The proofs of concept and efficacy of many vaccine candidates and therapeutics expressed in plants have been reported (see reviews[9],[10],[11],[12],[13]).

 4. Rapid acceleration and scalability

The currently available plant-based technologies for recombinant protein production include stable nuclear expression, stable chloroplast expression, transient expression, and suspension cultures. The stable transformation in nucleus or chloroplast can be achieved by Agrobacterium-mediated transformation or particle-bombardment whereas transient expression may be achieved by agroinfiltration or by using plant viruses. The stable plant suspension cultures can also be used for protein production by dispersing undifferentiated clusters of plant callus in a liquid medium that can be quickly propagated in bioreactors[14]. Each method has its own advantages and can be selected based on the nature of the target molecule. In the present scenario, the production of recombinant biopharmaceutical proteins through plant expression system seems to be reliable to deal with the pandemic situation. Cost and scalability are considered as the major advantages during the early stages of plant molecular farming technology, but now the rapid protein production by transient expression offers a faster vaccine production system. Transient expression system mediated by infiltration with Agrobacterium tumefaciens or with viral vectors is the method of choice especially during epidemic situations to produce adequate quantities of recombinant proteins rapidly in less than a month. The latest advances in transient expression results in a high-level accumulation of recombinant proteins, that can meet the industrial-level protein production[15],[16]. The manufacturing of biopharmaceuticals in plants could be a low-tech option that presents an unprecedented opportunity to address the demand for recombinant proteins in low and middle-income countries in the area of diagnostics as well as biologics[17]. The potential of commercial application of plant molecular farming and its importance to benefit the poor in developing countries has been reviewed here[18],[19].

 5. Future perspective

The importance and the role of plant-made biopharmaceuticals in the fight against COVID-19 has been extensively commented elsewhere[20],[21],[22]. The existing concept of producing effective immunogenic vaccine candidates in plants is boosting the plant molecular farming community towards COVID-19 vaccine development. Our group is currently investigating the potential of plant expression systems in making SARS-CoV-2 vaccines and therapeutic monoclonal antibodies by expressing recombinant chimeric proteins, sub-unit proteins, virus-like particles, and other biologics[23]. We are also evaluating the possibility of using plant-produced SARS-CoV-2 recombinant protein as a diagnostic reagent for developing a rapid diagnostic test kit in Thailand. Moreover, the plant-based pharma companies such as Medicago (Canada), Kentucky BioProcessing (USA), and iBio (USA) have proposed virus-like particle and subunit-based vaccine production in plants[20]. Further research in this direction is highly needed to accelerate the fight against this pandemic. If plant-produced vaccine candidates or monoclonal antibodies are shown to be efficacious, the substantial investments along with the well-directed regulatory framework would be helpful to realize the benefits of plant expression system in addressing the demand for recombinant biopharmaceuticals, especially during an infectious disease outbreak. We believe that the plant production system can be more attractive to the resource poor or developing countries who can utilize the cost-effective production of commercially viable recombinant proteins. Further, the plant-based technology is easy to transfer and promote regional manufacturing of protein products at relatively low-cost.

 Conflict of interest statement

The authors declare that there is no conflict of interest.


The financial support of Second Century Fund (C2F), Chulalongkorn University is greatly acknowledged.

 Authors’ contributions

Conceptualization, B.S. and W.P.; literature review, B.S.; writing-original draft preparation, B.S.; writing-review and editing, B.S. and W.P.; funding acquisition, W.P. All authors have read and agreed to the published version of the manuscript.


1Malla A, Shanmugaraj B, Ramalingam S. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): An emerging zoonotic respiratory pathogen in humans. J Pure Appl Microbiol 2020; 14(Suppl 1): 931-936.
2World Health Organization. Coronavirus disease (COVID-19) dashboard. 2020. [Online]. Available from: [Accessed on 10 November 2020].
3Shanmugaraj B, Siriwattananon K, Wangkanont K, Phoolcharoen W. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol 2020; 38: 10-18.
4Obembe OO, Popoola JO, Leelavathi S, Reddy SV. Advances in plant molecular farming. Biotechnol Adv 2011; 29: 210-222.
5Hiatt A, Cafferkey R, Bowdish K. Production of antibodies in transgenic plants. Nature 1989; 342: 76-78.
6Tschofen M, Knopp D, Hood E, Stöger E. Plant molecular farming: Much more than medicines. Annu Rev of Anal Chem 2016; 9: 271-294.
7Menary J, Hobbs M, Mesquita de Albuquerque S, Pacho A, Drake PMW, Prendiville A, et al. Shotguns vs lasers: Identifying barriers and facilitators to scaling-up plant molecular farming for high-value health products. PLoS One 2020; 15: e0229952.
8Shanmugaraj B, Malla A, Phoolcharoen W. Emergence of novel coronavirus 2019-nCoV: Need for rapid vaccine and biologics development. Pathogens 2020; 9: 148.
9Daniell H, Singh ND, Mason H, Streatfield SJ. Plant-made vaccine antigens and biopharmaceuticals. Trends Plant Sci 2009; 14: 669-679.
10Chan HT, Daniell H. Plant-made oral vaccines against human infectious diseases-Are we there yet? Plant Biotechnol J 2015; 13: 1056-1070.
11Rybicki EP. Plant-made vaccines and reagents for the One Health initiative. Hum Vacc Immunother 2017; 13: 2912-2917.
12Rybicki EP. Plant molecular farming of virus-like nanoparticles as vaccines and reagents. WIREs Nanomed Nanobiotechnol 2020; 12: e1587.
13Shanmugaraj B, Bulaon CJ, Phoolcharoen W. Plant molecular farming: A viable platform for recombinant biopharmaceutical production. Plants 2020; 9: 842.
14Moon KB, Park JS, Park YI, Song IJ, Lee HJ, Cho HS, et al. Development of systems for the production of plant-derived biopharmaceuticals. Plants 2020; 9: 30.
15Zischewski J, Sack M, Fischer R. Overcoming low yields of plant-made antibodies by a protein engineering approach. Biotechnol J 2016; 11: 107-116.
16Buyel JF. Plant molecular farming-Integration and exploitation of side streams to achieve sustainable biomanufacturing. Front Plant Sci 2018;9: 1893.
17Twyman RM, Stoger E, Schillberg S, Christou P, Fischer R. Molecular farming in plants: Host systems and expression technology. Trends Biotechnol 2003; 21: 570-578.
18Ma JK, Christou P, Chikwamba R, Haydon H, Paul M, Ferrer MP, et al. Realising the value of plant molecular pharming to benefit the poor in developing countries and emerging economies. Plant Biotechnol J 2013; 11: 1029-1033.
19Schillberg S, Raven N, Spiegel H, Rasche S, Buntru M. Critical analysis of the commercial potential of plants for the production of recombinant proteins. Front Plant Sci 2019; 10: 720.
20Capell T, Twyman RM, Armario-Najera V, Ma JKC, Schillberg S, Christou P. Potential applications of plant biotechnology against SARS-CoV-2. Trends Plant Sci 2020; 25: 635-643.
21Rosales-Mendoza S. Will plant-made biopharmaceuticals play a role in the fight against COVID-19? Expert Opin Biol Ther 2020; 20: 545-548.
22Rosales-Mendoza S, Márquez-Escobar VA, González-Ortega O, Nieto-Gómez R, Arévalo-Villalobos JI. What does plant-based vaccine technology offer to the fight against COVID-19? Vaccines 2020; 8: 183.
23Rattanapisit K, Shanmugaraj B, Manopwisedjaroen S, Purwono PB, Siriwattananon K, Khorattanakulchai N, et al. Rapid production of SARS-CoV-2 receptor binding domain (RBD) and spike specific monoclonal antibody CR3022 in Nicotiana benthamiana. Sci Rep 2020;10: 17698.