Exploring Latest Developments and Future Considerations on Anti-Covid-19 Drug Discovery: A Systematic Review Based on Current Evidences
Narasimha Raghavendra* and Leena V Hublikar
Department of Chemistry, Jabin Science College (Autonomous), India
Received Date: 08/08/2020; Published Date: 19/08/2020
*Corresponding author: Narasimha Raghavendra, Department of Chemistry, K.L.E. Society's P. C. Jabin Science College (Autonomous) Vidyanagar, Hubballi-580031, India
Cite this article: Narasimha Raghavendra and Leena V Hublikar. Exploring Latest Developments and Future Considerations on Anti-Covid-19 Drug Discovery: A Systematic Review Based on Current Evidences. Op Acc J Bio Sci & Res 4(1)-2020.
A novel COVID-19 is β-corona virus responsible for the SARS-COV-2 pandemic. WHO listed COVID-19 as a potential universal threat due to high basic reproduction number, lack of scientifically approved drugs, high mortality and vaccines for SARS-COV-2. Hence, many scientists are racing on the investigation of antiviral drug for COVID-19. Several methods and drugs such as chloroquine, hydroxy chloroquine, favipiravir, remdesivir, arbidol, Lopinavir/ Ritonavir, Remdisivir, Ribavirin, Sofosbuvir, and several medicinal plants are currently under clinical trials to screen their safety and efficiency in the treatment against COVID-19. Some interesting results have been successfully achieved so far. Present article summarizes the potential efficacy of anti-COVID-19 agents. The information reported in this article provides a strong platform to intellectual groundwork for future development of antiviral agents and vaccines.
keywords: COVID-19; Chloroquine; Hydroxyl Chloroquine; Medicinal plants; Antiviral
Two thousand nineteen is the era of coronavirus. The micro-organism which made the whole world to be blocked. The mankind is fighting against the smallest enemy, the micro-organisms every time. But, the things become more crucial when these micro-organisms cause of disease by means of air, touch and social contact of the population, which may not be under the control of civilian. Micro-organisms are the living organisms which could be able to observe through a microscope. But the viruses are smaller than the micro-organisms, so called as microbes, and are not alive in the air until it gets the host for replication [1-3]. Smallest of all the microbes are the viruses. These are unique because, until they enter into the other living cell, they do not multiply. These viruses made up of small bits of genetically active codes of DNA or RNA, embedded in the protective covering of proteins, called as Capsid. Further, these Capsids are covered by envelops, a spiky coatings. Viruses are existed only to multiply, when they attach to the host cell, and get replicated with its own genetic material, after this virus leaves the host cell by Lysis or by budding mechanisms [4-8]. Different types of viral infections are shown in the following (Table 1).
Table 1: List of viruses and its adverse effects.
The above viral diseases are classified as food borne, neurological infections, cutaneous infections, hemorrhagic infections, respiratory infections ,sexually transmitted and some other infections. Out of which, air, touch, sneeze borne respiratory infections are highly dangerous. Severity leads to the death of the living organism. Genetic material inside their shell is needed for their reproduction at host sites. With the help of medication, it is very difficult to fight against these viruses. Our immune system is to be disciplined by vaccinations of immunity boosting food items, so that we can protect our body avoiding infections [9-13]. Some viruses may help the host cells to fight against the other infections. Also being genetic materials itself, they are also used by biomedical researchers to insert genes in the cells. Century's greatest outbreak is of Covid -19. The novel Coronavirus Disease (COVID-19) emerged in Wuhan, China during December-2019 and then rapidly spread worldwide. This virus spreads worldwide undiagnosed easily, transmitted uncontrollably. Transmission of these viruses is possibly by contamination of objects and by coughing and sneezing. These diseases heal by itself and some common medications preferred are pain relievers, cough suppressants. Most of the respiratory diseases are from virus containing RNA genetic core, contains ribonucleic acid. This intern enclosed in the protein coating, called Capsid. Enveloping cover to Capsid is a glycoprotein, which helps to enter into the host cell by attaching through this [14-20]. In this regard, this review article summarizes latest developments and future considerations to treat against COVID-19. The steps followed in this review article are shown in Figure 1.
Figure 1: Steps followed in this review article.
Treatment Of Covid-19
Cross section study was conducted during the period From January till December 2019 on 100 patients attending King Faisal Medical Complex in Taif, presented with symptoms of gastrointestinal trouble (i.e., nausea, vomiting, loss of appetite, passage of loose stool, passage of mucoid stool, and abdominal pain). Patients had recently received anti-parasitic medications were excluded from this study.
All these examples show that it is important to be able to match the basic scientific laws within our profession with the working principles of the relevant medical devices and machinery and the systems connected to them. When combined with a solid theoretical know-how infrastructure and professional practice experience and systematic work, the design and production of these machines will be possible in our country. Cardiovascular, Cardiovascular Surgery, Orthopedics, General Surgery, Diagnosis - Imaging and Navigation, Neurology, Gastro-Intestinal Diseases, Ophthalmology, Internal Diseases, Oncology, Dermatology and many other medical departments in the department of health care at the stage of diagnosis and treatment of patients In the most general sense, the examples in the following paragraph can be given to give an idea for the devices and machines used.
Blood pressure measuring device, computer tomography devices, MR devices, PET / CT, x-ray devices, cardiograph devices, dialysis machines, steam autoclaves, sterilizers, artificial organs, artificial tissue, artificial blood, blood analysis devices, respiratory function device, mammography, ECG devices, various pumps, heat exchangers (heat exchangers), ultrasound devices, manometers, stethoscope surgical instruments, orthopedic implants, dental implants, chemical extraction for drug production, supercritical extraction, injectors, flow meters, refrigerators, medical refrigerators, freezers, operating table, operating room lighting and equipment, medical gas installation, operating room - hospital ventilation, patient room heating-ventilation-air conditioning devices, passive cooling systems (especially for tomography, MR devices etc.), injectors, catheter, weighing, scale, heater, patient beds, stretcher, band aj, tourniquet, anesthesia devices, ventilators, respirators, baby incubators, pacemaker systems, micropipettes, bedside monitors, radio frequency devices, serum bags-bottles, extractors, burettes, beakers, precision scales, electric mobile surgical aspirators, electrical safety test, endoscopy devices and systems, medical device calibration, quality management system applications for the health system, heart - lung pumps, infusion and perfusion pumps, vacuum meters, surgical robots and robotic surgical systems, nanoroboots, angio devices, stent manufacturing, tissue engineering products, biosensors, bone densitometers, dental and jaw x-ray and dentistry devices, electronically adjustable patient chair etc., serum pumps, hot-cold compresses, patient body heaters and coolers, lead gowns, life support units, emergency aid and ambulance vehicles and their internal Names, blood glucose meters, photodynamic therapy devices, physiotherapy devices, prosthetic leg - arm, tissue engineering applications, stem cells, implant batteries, optical imaging devices, optical diagnosis and treatment devices, devices used in eye diseases and treatment, microscope etc., acoustic diagnosis and treatment devices, image-supported therapy devices, neuro-optical stimulation devices, laboratory automation, rehabilitation robots, wheelchairs, digital modeling, virtual reality systems, wireless monitoring systems, mobile phone-network-based devices, computer-equipped devices and medical IT systems, nan-technological devices, are the examples of devices and machines frequently used in the diagnosis and treatment of patients within the scope of health services. There are also a variety of thermodynamic systems used in the fields of machinery, chemical and energy engineering, and various medical techniques used to obtain the active substances of drugs through various plants. In addition, the realization of medical technique applications is one of the most important main factors expected from the productive engineer of our age.
"Medical Technique" Many scientists going abroad from Turkey in the past year have undertaken serious issues success of our people. A team of different engineering and basic scientists have succeeded in making artificial brain tissue in an interdisciplinary study in the United States. Again, another scientist from our country who is currently working in the USA has succeeded in making an extremely low-cost portable blood test device that can easily analyze and transfer data by connecting to his mobile phone and has been awarded the young scientist of the year. Many successful studies for diagnosis and treatment for cancer and similar diseases are also ongoing. There is also a wearable pacemaker system developed and produced by a Turkish scientist working abroad. All our scientists mentioned herein, engineering and basic sciences in various branches in Turkey, whether charged, has continued graduate or complete their education are people who are moving towards an academic career.
Table 2: Binding energies of approved drugs in kcal/mol .
Where, N3 or RZS= ligands.
B. Cao et al.  reported the influence of Lopinavir–Ritonavir drug in 99 hospitalized COVID-19 patients. Out of 199 patients, 100 were assigned to standard-care group and remaining 99 to the lopinavir–ritonavir group. Mortality in the lopinavir–ritonavir and standard-care is similar at 28 days (19.2 % vs.25 %; difference, -5.8 % point; 95 % confidence interval, -17.3 to 5.7). Gastrointestinal negative events were more frequent lopinavir–ritonavir group and severe negative events more common in standard-care group. The treatment through Lopinavir–ritonavir was stopped early in thirteen patients due to adverse events. No positive effects were screened from lopinavir– ritonavir beyond standard care. Future clinical trials in COVID-19 patients may help to confirm the opportunity of treatment benefit.
The use Baricitinib for treating SARS-CoV-2 is also reported in the literature. The impending for combination therapy with this drug is very high due to low plasma protein binding capacity and minimal interaction with drug transporters and CYP enzymes. In addition, there is the possible potential for combining this drug with remdesivir, ritonavir, and lopinavir (direct acting antivirals) is currently employed in SARS-CoV-2 outbreak. Because, it has less interaction with CYP enzymes. Combination of this drug with direct acting antivirals may reduce the viral replication, aberrant host inflammatory response and viral infectivity .
Literature study also shows that, use of Chloroquine and hydroxychloroquine are the available weapons against COVID-19. The activity of hydroxychloroquine on virus is almost same as that of chloroquine because of mechanism action of Chloroquine and hydroxychloroquine is identical. Previously these compounds show good inhibition results against SARS-CoV. The adverse effect hydroxychloroquine is less compared to Chloroquine. Hence, hydroxychloroquine is the first choice to deactivate COVID-19. For optical treatment, it needs to manage loading dose followed by a maintenance dose. The important results chloroquine and hydroxychloroquine on corona virus is shown in Table 3 [25-34]. In this table, CCID50= 50% cell culture infectious dose, EC50= 50% effective concentration (mean ± S.D.), GFP= green fluorescent protein, HCoV= human coronavirus. and S.D= standard deviation.
Table 3: Effects of organic compounds against coronaviruses.
The antiviral drug IFN-α can be included in the treatment of novel coronavirus at a dose of 5 million U for adults, two times per day through a method of vapor inhalation. The two drugs lopinavir/ritonavir can be used at a dose of 400 mg/100 mg, two times per day. Ribavirin drug should be administered by intravenous infusion method at a dose of 500 mg combined with lopinavir/ritonavir or IFN-α. Further, Chloroquine phosphate, chloroquine and Arbidol are administrated at a dose of 300 mg, 500 mg and 200 mg for adults respectively. The precise method for administration of lopinavir/ritonavir, Chloroquine, Chloroquine phosphate, and Arbidol is oral. The duration of treatment should not exceed more than ten days. The safety and efficiency of these species in treatment against COVID-19 need to be verified for further preclinical and clinical studies (trials) . Latest study shows that, COVID-19 recovered patients have high neutralizing antibody could provide an important source of convalescent plasma. Previously, patients recovered from various infections can be successfully used to inhibit H1N1 influenza, Ebola, middle East respiratory syndrome, and SARS-CoV-1. The convalescent plasma greatly hinders the viremia. Hence, studying the response of antibody during COVID-19 infection provides strong support for the use of convalescent plasma therapy .
The author Elfiky  reported the potential property of Remdesivir, Ribavirin, IDX-184, and Sofosbuvir against the COVID-19 through computational approach. These drugs can be employed against new strain of COV’s as nucleotide inhibitors. GTP derivatives can also be used as efficacy inhibitors against novel coronavirus. Tocilizumab greatly suppress the activation role of COVID-19 and enhance clinical symptoms. The results show that, CT opacity changes, hypoxygenmia, and symptoms were significantly enhanced after treatment with this drug in COVID-19 patients without any adverse reactions. Further, the results presented in the Figure 2 and Table 4 supports the new therapeutic strategy for novel coronavirus disease .
Figure 2: Chest CT before and after Tocilizumab .
The carboxyl and amino groups are the main functional groups in the COVID-19, which causes severe infection to human cells. The hydroxyl plays vital role in the deactivation of COVID-19. The synthetic species have adverse effects on human species, hence plant ingredients gains interest. The licorice contains rich sources of green chemicals such as isoliquiritin, glycyrrhetic acid, glycyrrhizin, and liquiritin, which reduces the effect of virus on living creatures through esterification process. The nano membrane produced from licorice has antiviral property. Further, the hydroxyl groups of plant extract species can be employed to enhance the immunity power of human is under process. The other extract species such as ginseng, ginger, astragalus, sambucus, and garlic can show antiviral characteristics against COVID-19 .
Some medicinal species such Psorothamnus arborescens, Myrica cerifera, Hyptis atrorubens Poit, Phaseolus vulgaris, Phyllanthus emblica, Fraxinus sieboldiana, Camellia sinensis and Amaranthus tricolor as efficacy anti-COVID-19 candidates to inhibit novel corona virus. The molecules which are in lead for drug development and optimization to combat novel COVID-19 is shown in Table 5 .
The binding energies of some medicinal compound species such as allicin, gingerol, zingerol, epicatechin-gallate, catechin, curcumin, oleuropein, apigenin-7-glucoside, naringenin, demethoxycurcumin, luteolin-7-glucoside, quercetin, , kaempferol, , lopinavir, and nelfinavir, are -4.03, -5.38, -5.40, -6.67, -7.24, , -7.05, , -7.31, -7.83, -7.89, -7.99, -8.17, -8.47, -8.58, -9.41, -10.72, and -8.37 respectively. The compounds epicatechin-gallate, catechin, curcumin, , oleuropein, , apigenin-7-glucoside, demethoxycurcumin, and luteolin-7-glucoside compounds act as efficacy anti-COVID-19 agents. Additional research is required to find out their potential anti-viral use .
Table 5: Important plant extract species screened against COVID-19 3CL pro receptor with docking score and residues.
In addition to synthetic drug identification and exploration of natural medicine against novel virus is also important. Ayurveda is the ancient Indian rich culture of lifestyle, which was followed by each and every one of that era. Now a days we are following these as our medication routes of keeping health and body in balance. Word “AYUSH”means “life ” and “ VEDA ” means “Science”,this is the science of life which focuses on the healthier lifestyle. Diseases begin with an imbalance of consciousness in a leading life. Preventive and therapeutic approaches are fundamentals of Ayurvedic treatment .Because of climatic ,age - birth issues ,genetic imbalances largely define the emotions of persons. Stress is the main cause of illness. Maintaining balance among five basic elements of human body, namely, earth, water, fire, air, vacuum, and we achieve proper health. Anybody can increase body’s own capacity to enhance immunity system for fighting against viruses and allergens which can attack the body through respiration. Amongst God’s gifts to mankind, immunity power to human body, amazing. It restores itself for many day today infections, according to food we take, thus our immunity depends on the food we eat. Indian history got rich sources of food items to boost the immunity. The phytochemical present in the herbal food extracts helps in achieving it.
Every house’s kichen of the India had these food items and they aware of their uses seasonally.Some of them are Cumin, Honey, Ginger, Garlic, Cardmom, pepper, Turmeric, and Coriander. Another amazing health benefits are expected from Herbs. Since hundred years herbal therapy has been adopted for good health and assists the immunity system of the body. Around the world these medicinal plants focuses on herbal remedies for diseses. As said by the researchers amongst 4000 plant species, 30000 species were identified with alkaloids. Recently, scientific researches confirmed the treatments of various viral diseases and also a mechanism for their theraupetic actions,for plants like ,Boerhavia diffusa, Eclipta alba and Phyllanthus amarus. These plant extracts have greater capacity to cure many virus diseases. Some plant like, A. indica, Curcuma longa, Punica granatum, O. sanctum, and Carica papaya; also have greater potential for fighting against viral disorders. Phytosueticals of extracts of plant species like,Sambucus nigra and Caesalpinia pulcherrima, shows specific antiviral activities proven scientifically [42-51].
In this paper, we gave an overview of latest advancements in the treatment against COVID-19 disease. This novel virus spread through close personal contact and respiratory droplets. The currently available and efficiency of some synthetic and natural antiviral drugs are discussed in this review article. Future considerations for the development of effective antiviral drug is also reported in this paper. The efficiency of potent antiviral agents needs to be additional validated by current clinical trials.
Conflict of Interest
Authors declare no conflict of interest.
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