Targeting SARS-CoV-2 with therapeutic monoclonal antibodies

Sadique Hussain

1School of Pharmaceutical Sciences,Jaipur National University,Jagatpura 302017,India.

Background

COVID-19 was initially found in Wuhan,China,in December 2019,and was later designated a pandemic by the World Health Organization (WHO) [1].Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)quickly spread over the planet due to its great potential for human-to-human infection,causing significant harm to global health and worldwide trade.It is the 7thmember of the Coronaviridae family known to infect humans,transmitted by direct contact COVID-19 patients,and results in breathing problems,cough,chest tightness,disorientation,fever,respiratory distress,or dyspnea,as well as myalgia and asthenia[2].It is mostly a respiratory illness that also affects other organ systems such as the cardiovascular(CV),gastrointestinal(GI),kidneys,and neurological system[3].SARS,Middle East Respiratory Syndrome(MERS),and the newly revealed SARS-CoV-2 are the well-known CoV strains[4-5].

MAbs treatment has recently acquired a lot of attention.MAbs recognize particular epitopes in the target antigen and bind to them.MAbs were originally primarily utilized to develop diagnosis;medicinal implications were constrained by the immunogenic capabilities and low efficacy linked with murine antibodies due to the lack of effector activity.Following that,modified antibodies containing a murine variable domain and a human constant domain were developed and demonstrated to have fewer side effects while maintaining binding ability,leading to the approval of chimeric MAbs for a variety of indications,including infectious diseases,genetic diseases,tumor,allergic conditions,and so on[6].Therapeutic MAbs for COVID-19 therapy have been created at a breakneck speed that has never been seen before in any illness.Since the discovery of MAbs,the licenses were acquired in a record time of just 10 months,involving 3 to 4 months of clinical-grade MAbs manufacturing[7].

Celltrion,AstraZeneca,and Regeneron are among the pharmaceutical firms that support the development of MAbs as a therapy for COVID-19.The very first human study to cure COVID-19 is now ongoing,with the medication company "Lilly" using LY-CoV555 neutralizing MAbs against the spike protein.The neutralizing antibody LY-CoV555,at a dosage of 2800 mg,appeared to hasten the normal fall in viral load,but the two doses(700 mg and 7000 mg)did not.Bamlanivimab and Casirivimab-Imdevimab are new virus-neutralizing MAbs that have just been approved for the management of mild to moderate nCoV infected outpatients who are at an increased risk of getting to a serious infection.Early therapy may also be effective in halting the development of infection in highly infected patients.However,FDA granted an emergency use authorization(EUA)for Imdevimab and Casirivimab to be used jointly in adults and children with mild to moderate COVID-19[8-11].New SARS-CoV-2 viral variants have just been discovered.Mutations in the virus's DNA give rise to these variations.MAbs are still effective against the B.1.1.7 form of SARS-CoV-2.Certain mutations,though,may produce alterations in the spike protein,which might impair the efficacy of presently offered MAbs[12-13].Bamlanivimab,which targets SARS-CoV-2 spike protein,has been suggested for use in patients 10 days after the beginning of symptoms,however,it is ideally suited to be used in individuals soon after confirmed SARS-CoV-2 virological identification.Tocilizumab,an anti-IL-6-MAbs,is approved for the treatment of COVID-19 infected individuals who require ventilator support.On a broad level,when it comes to infectious diseases,there are three distinct indications for their use:treatment of infected individuals,prophylaxis for high-risk individuals for patient-level outcomes,and prophylaxis to interrupt transmission in the average-risk population for population-level outcomes[14].The large percentage of MAbs discovered so far address the spike protein's receptor-binding region,which permits SARS-CoV-2 to interact with the ACE 2 receptor.Neutralizing antibodies are expected to target additional areas of the spike protein as well,based on the current understanding of SARS-CoV and MERS-CoV.The efficacy of neutralizing MAbs in vitro in several cell culture tests is a crucial property utilized to assist identify MAbs with therapeutic application potential[15].

Even though MAbs are amongst the most rapidly increasing medication categories in the contemporary age,the exact mechanism through which they acquire their medicinal impact remains unknown.With therapeutic MAbs,any physiological reaction or result is dependent on many factors.Antigen cell surface density,tissue distribution,as well as the specificity,avidity,and isotype of any particular MAb,all play a significant influence.Attempts are being undertaken to address restrictions and increase therapeutic potential,and bioengineered human antibodies are showing new potential following chimeric and humanized MAbs[16].

Conclusion

As a consequence of the COVID-19 outbreak,clinical development and data review have been hastened,leading to speedy regulatory assessment and approval.Genomic characterization of developing variations of nCoVs has permitted the fast production of efficient post-exposure prophylactic neutralizing MAbs in tandem with vaccine development and therapeutic MAbs.The results of real-world research in high-risk groups will determine how these SARS neutralizing antibodies will be employed in clinical practice.

The first human trial to treat COVID-19 is currently underway,with the pharmaceutical company "Lilly" using LY-CoV555 neutralising MAbs against the spike protein.Bamlanivimab and Casirivimab-Imdevimab are two novel virus-neutralizing MAbs that were recently licenced for the treatment of mild to moderate nCoV-infected outpatients who are at risk of developing a severe illness.Early treatment may also be useful in preventing infection in those who are already infected.

Competing interests

The authors declare no conflicts of interest.

Abbreviations

WHO:World Health Organization;SARS-CoV-2:syndrome coronavirus 2;CV:cardiovascular;GI:gastrointestinal;MERS:Middle East Respiratory Syndrome.

Citation

Hussain S.Targeting SARS-CoV-2 with therapeutic monoclonal antibodies.Precis Med Res 2021;3(4):18.https://doi.org/10.53388/PMR20210018.

Executive editor:Nuo-Xi Pi.

Received:15 November 2021;Accepted:02 December 2021;Available online:07 Decemberr 2021.

©2021 By Author(s).Published by TMR Publishing Group Limited.This is an open access article under the CC-BY license.(http://creativecommons.org/licenses/BY/4.0/)

Table 1 Phase 2,3,and 4 trials of monoclonal antibodies are underway[17-19].

To summarise,MAbs are and will likely remain key treatment alternatives in the 21stcentury,not only for SARS-CoV-2 but also for other infectious diseases.MAbs that are extremely effective,can be created at a fraction of the present cost,and have a defined benefit group should be the focus of research.