**8. Adopted cure strategy**

Worldwide scientist and physicians started major campaign to understand the emergence of the disease and its possible antiviral treatment by drug development or therapeutic agents or developing vaccines. As of now there is no specific therapeutics agent or vaccine approved to cure COVID-19 patient in clinical procedure. Due to limited clinical and basic research information, most of the clinical trial/ manifestation follows basic symptomatic treatment protocol and supportive care which was followed for curing SARS and MERS patients [45]. The strategies of SARS-CoV and MERS-CoV therapy or antiviral drug have been extrapolated for the treatment of COVID-19 (**Table 1**). Most of the hospitalized infected patient have following status; (i) among the admitted patients, 23%–32% enters into ICU, (ii) 17%–29% feels critical respiratory failure (iii) ~7–8% were discharged and (iii) ~1% reported death. S-protein of COVID-19 has much similarity (in structural as well as replication procedure) with SARS and MERS protein and hence most of the articles reported broad spectrum antiviral activity of remdesivir, baricitinib, and chloroquine as the clinical trial antiviral drug [19] (**Figure 5**). Remdesivir demonstrated effectiveness for curing COVID-19 in USA [46]. Nucleotide type of remdesivir drug

*Epidemiology, Pathogenesis, and Healing Strategies of COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.96200*


#### **Table 1.**

*Target protein related to nCoV-19, SARS-CoV and MERS-CoV and possible drug proposed for prevention (data taken from reference [34–51]).*

#### **Figure 5.**

*structure of viral entry inhibitor (a) remdesivir, (b) ribavirin, (c) IDX-184, (d) chloroquine, (e) hydroxycholoroquine, and (f) camostat mesylate.*

assisted to premature termination of RNA chain in host cell. On the other hand, ribavirin is a guanosine analogue mostly used for treating chronic hepatitis C [47]. However, study finds suitable dosage of ribavirin might stop the replication spike protein RNA [47]. Lopinavir (a viral protease inhibitor) with its pharmacological booster ritonavir (LPV/R) initially proved to be useful for HIV, SARS-CoV, MERS-CoV treatment with the action of protease inhibitors. Recently study in South Korea reveals significant decrease in COVID-19 viral load after treating with (LPV/R) [46, 48]. Similar reduction in viral loading (associated with pneumonia related symptoms) was also observed after treating with arbidol [34]. Chloroquine and its hydroxy-analogue hydroxychloroquine demonstrated to be relevant for patient having diabetes with infected COVID-19 [14]. Researcher and scientific community stress more on 3CLpro, PLpro and RdRp protein target than other target possibly due to the most responsible proteases for COVID-19 replication and hence attractive targets for antiviral therapies. Further, one needs to understand, the possible action mechanism of existing drug on COVID-19 before being used. For example, arbidol can be used for fusion of virus-host cells to prevent virus entry into the host. The clinical trial of arbidol is in process [34]. Clinically approved camostat mesylate a possible inhibitor used (to reduce activity of TMPRSS2) for blocking the COVID-19 entry into human body [35]. Combination of tocilizumab and hydroxychloroquine found to be very effective for curing COVID-19 patient underwent kidney transplant surgery [49].

### **9. Role of biosensor devices**

Recently nanomaterial used for point of care diagnosis, therapeutics agent, or in vaccine development. Nanomaterial found to be the promising candidate for the modulation of viral infection cycle [4]. Especially, carbon quantum dots having size below 10 nm found to be a promising interferes for the viruses into the cells. Nanomaterial having different nanostructure offers multivalent character due to surface to volume ratio. Such multivalent properties facilitate several ligands to attach with virus. The viral-ligands interface blocks the entry of virus into the host cell [20]. Łoczechin et al. reported function of carbon quantum dot (CQD) as inhibitor for COVID-19 [52]. CQD synthesis itself from different precursor offer different level of inhibition strength to corona virus. Two different study of CQD synthesis from (i) citric acid/ethylenediamine and further conjugated by boronic acid, and (ii) 4-aminophenylboronic acid and phenylboronic acid offer 50% inhibition concentrations of EC50 = 52 ± 8 μg mL<sup>−</sup><sup>1</sup> and EC50 = 5.2 ± 0.7 μg mL<sup>−</sup><sup>1</sup> , respectively [52]. CQD inhibit growth of s-protein by fusion mechanism and stop replication process of S-protein by signal transduction mechanism or by interaction with cytosolic proteins [52]. Nanomaterial particles as therapeutic agent for stopping viral entry and subsequent replication of S-protein in host membrane may be an alternative of many existing treatment to avoid their side effects. For example, use of ribavirin and IFN as an antiviral drug for COVID-19 spike protein have many side effects including short-term memory loss, confusion, extrapyramidal effects and deficits in executive functions [20, 52].

Plasmonic biosensor working on the cumulative effect of plasmonic photothermal (PPT) and localized surface plasmon resonance (LSPR) transduction principle found to be another potential alternative diagnosis of COVID-19 [53]. Two dimensional (2D) gold nanoislands (AuNIs) functionalized with DNA receptors exploited as sensing of RNA gene sequence. Sensitivity of material can be enhanced to some order by direct thermoplasmonic heating to biosensor chip. The usable plasmonic heat to the chip has been generated by setting a particular plasmonic resonant frequency. Photon generated oscillation frequency modulated the electrons behavior on the surface of plasmon material which might be the crucial factor for detection of selective COVID-19 gene sequence from multi gene mixture. Enhanced plasmonic field at the nanostructures surfaces increases sensitivity of sensor by suppressing local variation like refractive index and molecular binding. Employing field effect transistor as biosensor for fast and accurate spike protein detection through nasopharyngeal swab has recently been reported by Seo et al. [54]. Graphene coated specific antibody has been used as sensing material for spike protein detection [54]. The spike protein directly not attached with graphene surfaces rather 1-pyrenebutyric acid N-hydroxysuccinimide ester was used as probe linker to conjugate protein structure on graphene surfaces. Such attachment of spike protein induced by 1-pyrenebutyric acid N-hydroxysuccinimide ester on graphene surface leading to changes in conductivity and subsequently in current through the FET structure

*Epidemiology, Pathogenesis, and Healing Strategies of COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.96200*

#### **Figure 6.**

*(a) showing conjugation of spike protein on to the surface of graphene via 1-pyrenebutyric acid N-hydroxysuccinimide ester (b) model showing spike protein on the surface (covered with graphene) of field effect transistor (c) FET sensor sensitivity in presence of SARS-COV-2 antibody and in absence of SARS-COV-2 antibody and (d) FET sensor sensitivity in MERS-COV and SARS-COV-2 (reproduce with permission [32]).*

(shown in **Figure 6 (a)** and **(b)**). The sensitivity which was measured by current fluctuation due to presence or absence of spike protein is shown in **Figure 6(c)** and **(d)**. The biosensor capable to detect down to 16 pfu/mL in cultural mode and 2.42 × 102 copies/mL in clinical sample [32]. The diagnosis method does not require sophisticated laboratory equipment and provide very high sensitivity with instantaneous measurements employing small volume of nasopharyngeal swab.

#### **10. Conclusions**

Like other epidemic, COVID-19 may also become seasonal, but at present one can only predicted about it not for sure. Meanwhile, to reduce the outbreak, it is required to have international collaboration with data sharing policies. Because, of the limited information, one can reuse the existing drugs as clinical trial for curing COVID-19 infection (based on the similarity of target protein with other coronavirus). Further, fight against COVID-19 requires the knowledge of computer science, medicine, health policy, environmental factors and risk management etc. Present situation imposes researcher and scientific community a number of research target viz.; (i) production of rapid point of care diagnosis (ii) enhancement in surveillance and monitoring (iii) design of new therapeutic agents and finally (iv) vaccine development. We can only reduce the transmission level up to certain extent but cannot be demolished completely. For complete cure one has to develop vaccine.

#### **Conflict of interest**

Author declares there is no conflict of interest.
